bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hair growth promoting effects of Geranium sibiricum L extract on human dermal papilla cell under glucocorticoid‐induced stress condition (830.18)
Authors: Lee Bog‐Hieu , Yu Miri , Choi Joo‐Yeon , Jeong Gi Hee 
Published: June 2021

The study investigated whether Geranium Sibiricum L extract(GSE) with high antioxidant activity has hair growth promoting effect in artificial stress condition or not. MTT assay and scratch migration assay were used for to determine the GSE effect on human dermal papilla cell(hDPC). To analyze hair growth promoting effect of GSE, we implemented Ki67 immunochemistry staining and cytokine(TGF‐β1 and HGF) analysis. Stress condition was induced using synthetic glucocorticoid (dexamethasone, DEX). GSE showed highest proliferation effect in 19.5 ppm(ug/ml) and migration effect of GSE was actively accelerated in 19.5 ppm as well. DEX treatment group appeared to be very low Ki 67 positive cells but GSE and DEX co‐treatment group exhibited Ki 67 positive cells more than normal condition(NC) group. Relative TGF‐β1 expression was the lowest in GSE group, while DEX group showed the highest TGF‐β1 expression. GSE and DEX co‐treatment group showed 25.8% lower TGF‐β1 expression than DEX treatment group. Relative HGF expression was the highest in GSE group. In DEX group, HGF expression was very low, but GSE and DEX co‐treatment group showed similar HGF expression to NC group. GSE and DEX co‐treatment group expressed 12 times more HGF expression level than DEX group. These results suggest that GSE promotes the proliferation and migration of hDPC possibly by suppressing TGF‐β1(hair growth inhibition cytokine) expression level, and elevating HGF(hair growth promoting cytokine) expression in stressful condition.Grant Funding Source: supported by Basic Science Research Program through the Natiional Research Foundation of Korea(NRF)
Protective immunotherapy against seasonal allergy in horses (834.2)
Authors: Venugopal Changaram , Prayaga Sudhirdas , Eades Susan 
Published: June 2021

The study objective was to evaluate the effectiveness of active and passive immunotherapy in horses affected with recurrent airway obstruction (RAO), using a newly developed peptide and antibodies to the peptide. This peptide is part of an endogenous protein and has a sequence homology to some common environmental allergens. RAO is a type‐I immediate hypersensitivity response involving reaginic antibodies (IgE and IgG), and is a model for human asthma. Our hypothesis is that a protective immune response to asthma can be induced by active vaccination or by passive immunotherapy. Five RAO‐affected horses with a history of seasonal RAO, transpulmonary pressure >15 cm of H2O, and a clinical score (CS) of 5 and above were selected. Either of the two doses of the antibody, 0.1 mg/kg or 0.2 mg/kg, was administered subcutaneously to 2 horses each. A third dose 0.3 mg/kg was given to the fifth horse. The peptide (0.1 mg/kg) was used to vaccinate two additional RAO‐horses. After closely watching them for 2 days, they were returned to the pasture. Blood samples were collected on day 0 (pre‐immune sample), day 1 and every 7th day for two months along with clinical scores. A dose related decrease in CS was observed in horses that received antibodies. The serum antibody titer was below detection levels by ELISA. The vaccinated horses showed significant protective antibody titer when the season arrived. The study suggests that protective immunotherapy early in the season has some therapeutic potential for RAO‐affected horses.Grant Funding Source: Supported by EHSP, LSU‐SVM
Influence of food allergy on the course of bronchial asthma in children (834.5)
Authors: Urazova S. , Turebaev D. 
Published: June 2021

Food allergy is a common type of allergy reactions in children. At the same time, there is little explored the impact of food allergy on the development and course of bronchial asthma in children.Objective: to study the characteristics and clinical manifestations of bronchial asthma in children.Material. 100 children with bronchial asthma associated with food sensitization (experimental group) have been examined. The control group consisted of 60 children with bronchial asthma, who had no manifestations of food allergy. The age of patients was from 1 year to 16 years.The results of the study.It is noted more previous (p <0,01) beginning bronchial asthma in children who had food allergens as the cause significant factors in its exacerbation in comparison to the control group. Bronchial asthma attacks in children with food sensitization were recorded in the experimental group was 1.8 times more than in control group. Severe bronchial asthma was noted in 2 times more often in children with food sensitization than in the control group. The higher level of total IgE (p<0,05) in children with bronchial asthma exacerbation to food antigens from 6 to 9 years of age was noted in comparison to control group. Gastroduodenit(38.2% and 41.3%) was dominated inthe experimental and the control group, respectivelyand eyunit, esophagitis in children with acute asthma were found in 2 times more likely than children in the control group.
Changes during development of COX 1 and 2 in heart, abdominal and thoracic aorta (837.11)
Authors: Acevedo‐Villavicencio Nallely , Arellano Monica , Ramirez‐Sanchez Israel , Mera‐Jimenez Elvia , Lopez‐Calderon Emilio , Guevara‐Balcazar Gustavo , Castillo‐Hernandez Maria 
Published: June 2021

Cyclooxigenase 1 and 2 have been related in the release of prostanoids that regulate the effect of various agonists as in the case of phenylephrine, but its unknown that how this enzyme is involved in the contractile response to phenylephrine age‐dependent. The aim of this paper is to analyze changes of COX 1 and 2 involvements in the contractile response to phenylephrine in the thoracic and abdominal aorta and coronary artery of pubescent, young and old rats. It has been describe that during development there are changes in the activity of some enzymatic pathways, in this work we analyze the change in the involvement of cyclooxygenase and PGs in the contractile effect of phenylephrine with age. Methods: we used male rats of 6, 16 weeks and 1 year of age. Rats were anesthetized with pentobarbital (50 mg / kg), after that we proceeded to obtain the thoracic aorta and abdominal aorta and the heart and they were placed in an isolated organ system where we proceeded to make concentration response curves to phenylephrine. On the other hand we obtain heart and aorta for the western blot analysis and the immunohistochemistry assay of COX 1 and COX 2. Conclusions: COX1 increase during development. On the other hand COX2 decrease in the elderly stage only in thoracic aorta.Grant Funding Source: COFAA / IPN
Studies of the neurochemistry underlying swimming forces in Daphnia magna (839.8)
Authors: Sneed Raesean , Beckman Matthew 
Published: June 2021

Daphnia magna are keystone species in freshwater lakes and ponds. Because they are consumed by fish in aquatic environments they are important to the health of freshwater bodies. Their ability to evade predation is central to their survival. Daphnids are also an emerging model organism in toxicogenomics and behavioral pharmacology. The major aim of this study is to understand the role that environmental temperature plays in shaping the neurochemistry underlying the maximum power stroke exerted by the second antennae—the mechanism for swimming in daphnids. In order to measure the forces produced by swimming daphnids we developed a low‐cost method for determining micronewton‐range swimming forces produced by tethered daphnids. To measure the power stroke, daphnids were tethered to custom‐made, calibrated force transducers composed of fine plastic filaments embedded in glass micropipettes held by a positioner. Two perspective video imaging was carried out to measure forces associated with swimming. Two populations of Daphnia magna were studied: one group was raised at 20°C and a second group was reared at 28°C. The data reveal an increase in the maximum power‐stroke among the daphnids raised at 28°C compared to 20°C. Further studies aim to delineate any neurochemical changes involved in this adaptation. These studies are providing insight into the role that environmental temperature plays in shaping the motor control and physiology of swimming behavior in Daphnia, a new model organism.Grant Funding Source: Supported by The Augsburg McNair and NorthStar STEM Programs and the Eppley Foundation for Research
Characterization of voltage‐operated and non‐voltage‐operated calcium channels in endothelin‐induced vasoconstriction of rat cerebral arteries (841.6)
Authors: Mamo Yohannes , Ziogas James , Soeding Paul , Angus James , Wright Christine 
Published: June 2021

Endothelin‐1 (ET‐1) is a potential mediator of the pathogenesis of cerebral vasospasm. This study analysed the role of voltage‐operated calcium channels (VOCC) and non‐VOCC in ET‐1‐ induced vasoconstriction of rat cerebral arteries.Rat isolated cerebral arteries (320‐430 µm i.d.) (anterior cerebral, middle cerebral, posterior communicating and basilar) were investigated using wire myography. ET‐1 concentration‐contraction response curves were constructed in arteries in calcium‐free medium or in the presence of nifedipine, NNC 55‐0396 or SK&amp;F 96365 to inhibit the L‐type VOCC, T‐type VOCC and non‐VOCC, respectively. The ability of these antagonists to reverse the ET‐1‐induced contraction was also tested.Neither inhibition of calcium channels nor removal of calcium altered the potency (pEC50) of ET‐1, but the maximum effects of ET‐1 (Emax) were variably attenuated. ET‐1 caused a small contraction (11‐22%) in calcium‐free solution. Nifedipine (1 µM) significantly decreased the Emax only in the middle cerebral artery, while NNC 55‐0396 (1 µM) and SK&amp;F 96365 (30‐100 µM) attenuated the Emax in all cerebral arteries. Combination of nifedipine with SK&amp;F 96365 more moderately decreased the Emax. Both nifedipine and SK&amp;F 96365 reversed the ET‐1‐induced pre‐contraction in all arteries.In conclusion, ET‐1 causes potent contraction by differentially activating both VOCC and non‐VOCC in rat cerebral arteries.
Rgs16 is an early marker of pancreatic ductal adenocarcinoma (842.7)
Authors: Ocal Ozhan , Heath Blake , Rivera Lee , Pashkov Victor , Swift Galvin , Brekken Rolf , Wilkie Thomas 
Published: June 2021

Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer related deaths. Limited progress has been made in developing effective therapy for PDA. Compounding this challenge has been the lack of a systematic and robust in vivo screen for effective drug combinations. Kras mutations (e.g. KrasG12D) are found in over 90% of human PDA and occur early in tumor progression. Protein kinase and G‐Protein Coupled Receptor (GPCR) signaling can initiate Ras activation. Regulators of G‐protein Signaling (RGS) proteins are coincidence detectors that can be induced by and integrate multiple inputs to feedback regulate GPCR signaling. We previously described Rgs16 expression during embryonic and postnatal pancreas development in pancreatic progenitors, endocrine cells and ductal‐associated cells. Here, we show that the Rgs16::GFP transgene is a KrasG12D dependent marker of all stages of neoplasia in the p48Cre; LSL‐KrasG12D; Cdkn2af/f PDA mice. Although KrasG12D is expressed in embryonic pancreas progenitor cells and in all mature acinar cells, Rgs16::GFP expression in tumors first emerges in ductal Pancreatic Intraepithelial Neoplasms as early as 12 days post birth. The distribution and intensity of expression is proportional to and coincident with tumor burden. Rgs16::GFP expression in acinar cells of distal lobes initiates only after tumor occlusion of proximal ducts. The gene expression signature of primary PDA cells in culture obtained via RNA‐seq is closely related to embryonic progenitors of pancreatic ducts and endocrine cells. PDA cells in culture are highly sensitive to the chemotherapic drug gemcitabine mediated cell death. In a proof‐of‐principle for drug screens, we find PDA weanling mice treated with gemcitabine and Nab‐paclitaxel for two weeks have significantly lower Rgs16::GFP expression and reduced tumor size and occurrence. Rgs16::GFP is a novel in vivo reporter of PDA progression and sensitivity to new drug regimens that inhibit Kras mediated oncogenesis.Grant Funding Source: Supported by NCI‐CA161624.
Ric‐8A deletion as tumor suppressor of oncogenic G‐protein alpha subunit alleles (842.8)
Authors: Patel Bharti , Tall Gregory 
Published: June 2021

Constitutively‐active Q209L (QL) mutations in Gαq and Gα11 were found in 83% of human ocular melanomas. Ectopically expressed Gα11‐QL drove metastatic melanoma from xenografted melan‐a cells. No therapeutics target the melanoma‐driving mutant G proteins. Ric‐8A and Ric‐8B are molecular chaperones required for Gα subunit biosynthesis and maintenance of cellular Gαq/11 levels. Blocking Ric‐8A function may represent a viable means to attenuate the abundance of mutant, oncogenic G proteins. To test this, we created a Ric‐8A conditional knockout mouse. Homofloxed Ric‐8A mouse embryonic fibroblasts (MEFs) were isolated and transduced by lentivirus to express Cre‐recombinase and induce a Ric‐8A knockout (KO). Dramatic decreases in endogenous Gαi/o and Gαq/11 subunit levels were observed in Ric‐8A KO MEFs. Ric‐8A KO and control MEFs were examined for known cytotoxicity elicited by Gα11‐QL overexpression. Cell growth rates were measured and correlated to cytotoxic cell death measured by lactate dehydrogenase activity in culture media. Ric‐8A induced KO in MEFs reduced expressed Gα11‐QL levels and rescued cytotoxicity. To study the effect of Ric‐8A gene ablation on suppression of GNA11‐QL‐driven mouse melanoma, a Ric‐8A homofloxed mouse with melanocyte‐specific, tamoxifen‐inducible Cre‐recombinase was created. Inducible Ric‐8A KO melanocytes were immortalized and stably transduced with GNA11‐QL. Melanocytes will be xenografted in immunodeficient mice to induce Gα11‐QL driven melanoma. The efficacy of tamoxifen‐induced Ric‐8A deletion in injected melanocytes (or derived tumors) to inhibit the Gα11‐QL‐dependent melanoma will be examined. Tumor growth rates, metastases, and Kaplan‐Meier survival analyses will be presented. We anticipate that Ric‐8A KO‐dependent Gα abundance decrease will attenuate oncogenic Gα11‐QL driven melanoma and increase survival. Our work will establish the tenability of Ric‐8A as a potential drug target for disease caused by mutant G proteins.Grant Funding Source: Supported by NIH grant RGM088242A
Metabolic control points in cancer (85.3)
Authors: Jones Russell , Faubert Brandon , Dupuy Fanny , Izreig Said , Boily Gino , Griss Takla , Samborska Bozena , Siegel Peter 
Published: June 2021

All cells must manage their energetic resources to survive. This is particularly true for cancer cells, which initiate changes in their cellular metabolism as they transition from a normal to a cancerous state. Tumor cells must engage pathways of cellular metabolism to generate the energy and biosynthetic intermediates required to support increased cell growth and division. In addition, for growing tumours, overcoming metabolic stress induced by nutrient limitation and/or hypoxia is a critical step for solid tumour growth. It is now appreciated that many of the predominant mutations observed in cancer also influence tumor metabolism as part of their mode of action. Here I discuss the role that cellular energy sensors ‐ notably the Liver Kinase‐B1 (LKB1) and the AMP‐activated protein kinase (AMPK) ‐ play in regulating tumor metabolism and adaptation to metabolic stress. We have found that the LKB1‐AMPK pathway negatively regulates aerobic glycolysis (the “Warburg effect”) in cancer cells, and that disruption of this pathway promotes a metabolic shift to aerobic glycolysis and supports increased cell growth. This metabolic shift is mediated by the hypoxia‐inducible factor‐1α (HIF‐1α), and silencing HIF‐1α reverses the biosynthetic and proliferative advantages conferred by reduced LKB1‐AMPK signaling. Finally, I will present evidence that AMPK activity is dynamically regulated in tumors to enhance pro‐growth metabolism, but that this pathway is required to maintain tumor cell viability in response to stress. Finally, I will discuss whether metabolic checkpoints serve “suppressive” or “supportive” roles in cancer development and/or progression.This work was supported by grants from the CIHR (MOP‐93799) and CCSRI (700586).
Cyclic AMP reverses the pro‐fibrogenic phenotype of cardiac myofibroblasts (850.3)
Authors: Aroonsakool Nakon , Yokoyama Utako , Lu David , Patel Hemal , Insel Paul 
Published: June 2021

Previous data have shown that increased cellular levels of cyclic AMP (cAMP) can prevent the transformation of cardiac fibroblast (CFs) into pro‐fibrogenic myofibroblasts (MyoFbs), a transformation that precedes increased extracellular matrix deposition and cardiac fibrosis. We have now investigated two additional roles for cAMP: 1) contribution to the MyoFb phenotype and 2) reversal of the MyoFb phenotype. We found that MyoFbs have lower cAMP content than do CFs, and in addition, have decreased mRNA and protein expression of isoforms of adenylyl cyclase (AC), including AC5 and AC6, the two major AC isoforms, and increased expression of several phosphodiesterase isoforms. Incubation of primary isolates of adult rat CFs with a pro‐fibrotic stimulus, TGFβ1 (10ng/mL, 48hr), prominently increases mRNA and protein expression of collagen Iα1, Iα2, III, α‐smooth muscle actin, plasminogen activator inhibitor‐1 and cellular contractile state. All these hallmarks of the fibrogenic state were reversed in MyoFbs incubated with 10µM forskolin (a direct AC activator). Furthermore, incubation with N6‐Phe‐cAMP (a PKA selective analog) also reversed the pro‐fibrogenic state. We conclude that MyoFbs have a lower level of cAMP and that increasing cAMP content can reverse their pro‐fibrotic state. Approaches to increase cAMP in MyoFbs may provide a means to treat cardiac fibrosis.Grant Funding Source: NIH
Cardiac myocyte‐specific overexpression of caveolin‐3 enhances β‐adrenergic signaling and response in young and aged mice (850.8)
Authors: Busija Anna , Roth David , Insel Paul , Patel Hemal 
Published: June 2021

Caveolins (Cavs) are scaffolding proteins essential to the formation of caveolae, membrane domains that compartmentalize numerous signaling molecules, including β‐adrenergic receptors (β‐ARs). A decrease in Cav proteins with aging may contribute to age‐associated loss in cardiac function. By contrast, mice with cardiac myocyte (CM)‐specific overexpression of Cav‐3 (Cav‐3 OE) have more caveolae in CMs and are protected from age‐associated cardiovascular dysfunction. β‐AR agonists increase inotropy and chronotropy but whether increased Cav‐3 expression alters β‐AR response as a means to preserve cardiovascular function with age is unknown. We treated Langendorff‐perfused hearts from young and aged transgene‐negative (TGneg) and Cav‐3 OE mice with the β‐AR agonist isoproterenol (Iso). Cav‐3 OE mice had augmented Iso‐stimulated inotropy (+dP/dt) and lusitropy (‐dP/dt) relative to TGneg, and CMs isolated from Cav‐3 OE mice have increased cAMP production and phospholamban phosphorylation in response to Iso. Moreover, aged (20‐22 month‐old) Cav‐3 OE mice have preserved β‐AR‐stimulated inotropy and lusitropy compared to age‐matched TGneg mice. Thus, increased expression of Cav‐3 enhances β‐AR‐promoted contractile function in both young and aged mice. Increase in Cav‐3 expression may be a way to enhance cardiac β‐AR response throughout the life span.Grant Funding Source: Supported by NIH HL107200
Coronary endothelial dysfunction induced by Nlrp3 inflammasome activation during hypercholesterolemia: beyond inflammation (851.13)
Authors: Zhang Yang , Li Xiang , Pitzer Ashley , Li Pin‐Lan 
Published: June 2021

Recent studies have shown that Nlrp3 inflammasomes function as a major intracellular molecular machinery to switch on the inflammatory response upon sensing danger signals such as elevated plasma levels of cholesterol during hypercholesterolemia (HC). The present study tested the hypothesis that endothelial Nlrp3 inflammasome activation has uncanonical direct actions on endothelial cells (ECs) producing endothelial dysfunction prior to or during inflammation, which contribute to vascular injury at early stages of atherogenesis. Endothelial dysfunction was assessed by evaluating endothelium‐dependent vasodilation (EDVD) in isolated, perfused and pressurized coronary arteries in response to bradykinin and acetylcholine. HC induced by poloxamer 407 impaired EDVD in Nlrp3+/+ mice, which was markedly ameliorated in Nlrp3‐/‐ mice. Pretreatment of coronary arteries with inflammasome products showed that IL‐1β or HMGB1 impaired EDVD in normal Nlrp3+/+ mice suggesting a detrimental effect of IL‐1β or HMGB1 on the endothelium. In contrast, HC‐induced impairment of EDVD in Nlrp3+/+ mice was attenuated when these mice were treated with caspase‐1 inhibitor WEHD or HMGB1 inhibitor glycyrrhizin, but not with IL‐1β receptor antagonist. Confocal microscopic analysis demonstrated that in Nlrp3+/+ mice, HC increased caspase‐1 activity and HMGB1 expression in coronary arterial endothelium, but did not alter the levels of IL‐1β or Mϕ marker F4/80. In cultured ECs, cholesterol crystals (CCs) activated Nlrp3 inflammasomes and increased caspase‐1 activity. Further, CCs impaired EDVD in coronary arteries from Nlrp3+/+ mice, but not in Nlrp3‐/‐ mice. Taken together, these results suggest that activation of endothelial Nlrp3 inflammasomes directly impair endothelial function beyond its canonical inflammatory effects such as Mϕ recruitment and T‐cell infiltration. This non‐inflammatory action of Nlrp3 inflammasome activation may initiate or exacerbate vascular injury during HC.Grant Funding Source: Supported by NIH grants HL057244, HL091464 and HL075316
Cardiovagal baroreflex sensitivity is improved in children with high blood pressure after a psychosocial intervention (852.1)
Authors: Klassen Stephen , Chirico Daniele , Hood Colleen , Wade Terrance , Cairney John , O'Leary Deborah 
Published: June 2021

The aim of this study was to assess the effectiveness of a Leisure and Well‐Being Model (LWM) psychosocial intervention on blood pressure (BP) regulation in children. Children with consistent BP 蠅 95th percentile and <90th percentile were grouped into high (HBP) and normal blood pressure (NBP) groups, respectively. Anthropometric data were collected along with five minutes of supine beat‐by‐beat BP and R–R interval. High frequency (HF; 0.15‐0.5 Hz) and low frequency (LF; 0.05‐0.15 Hz) power spectral indices were computed and transfer function analysis for the LF region was used to calculate baroreflex sensitivity (BRS). Pre and post‐test measures were taken one year apart. Results from 60 children (43 NBP, 17 HBP) indicated a three‐way interaction between intervention, BP status (NBP or HBP) and time (year 1 to year 2) independent of BMI (p=0.036). HBP participants receiving the intervention demonstrated an improvement in BRS from year 1 (11.4 ± 5.4 ms/mmHg) to year 2 (17.4 ± 8.5 ms/mmHg) compared to the HBP participants that did not receive the intervention (15.3 ± 8.5 ms/mmHg to 13.4 ± 6.5 ms/mmHg). These findings demonstrate that a LWM psychosocial intervention had a positive impact on BP regulation in children with elevated BP. These findings provide evidence of the importance of psychosocial determinants on autonomic regulation of BP in children.Grant Funding Source: Heart and Stroke Foundation of Ontario