bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oroxylin A induces relaxation of porcine basilar arteries via cGMP pathway
Authors: Tsai Andy Po‐Yi , Chen Mei‐Fang , Wang Mei‐Jen , Lee Tony Jer‐Fu 
Published: November 2023

The possible involvement of cyclic guanosine monophosphate (cGMP) and potassium channels in mediating oroxylin A (Oro‐A)‐induced relaxation of porcine isolated basilar arteries was examined. Oro‐A, a flavonoid isolated from the natural herb, Scutellariae baicalensis, is used widely for various diseases. Its role in regulating cerebral vascular functions, however, remains unclear. Results from blood vessel myography studies indicated that Oro‐A in a concentration‐dependent manner relaxed U46619 (a thromboxane A2‐receptor agonist)‐contracted basilar arterial rings. The relaxations, which were independent of the endothelial cells and perivascular nerve fibers, were inhibited by blockers for nonspecific potassium channels, preferential calcium‐activated potassium (BKca)‐channels, and preferential ATP‐sensitive potassium (KATP)‐channel. Also, Oro‐A‐induced vasorelaxation was drastically decreased in arteries pre‐contracted by high potassium. By using two‐electrode voltage clamp, Oro‐A, however, did not directly open the BKca‐ or KATP‐channels on oocytes from Xenopus leavis. Moreover, Oro‐A‐induced vasorelaxation was blocked by a soluble guanylate cyclase (sGC) inhibitor, but was not affected by inhibitors of adenylate cyclase or protein kinase A. In addition, concentrations of cGMP but not cAMP in endothelium‐denuded basilar arteries were significantly increased following incubation with Oro‐A. These results suggest that OroA increases synthesis of cGMP which then opens the BKca‐ and KATP‐channels on the smooth muscle cells of the basilar arteries causing relaxation. Together with its reported anti‐inflammatory effects, Oro‐A may be a promising compound for ameliorating cerebral neurovascular dysfunctions.Support or Funding InformationSupported by Ministry of Science and Technology of Taiwan, Tzu Chi Foundation, and Tzu Chi University
Perivascular Adipose Tissue Modulates the Anticontractile Effect of Cooling in the Rat Aorta
Authors: Rafique Yasmeen , Al‐Bader Maie , Oriowo Mabayoje 
Published: November 2023

The perivascular adipose tissue (PVAT) provides mechanical support for blood vessels and exerts an anti‐contractile effect. The present study was designed to investigate how PVAT and gender affect the anti‐contractile effect of cooling in the rat aorta. Aorta segments, with or without PVAT from male and female SD rats were used in this investigation. PE (10−9M – 10−5M) induced concentration‐dependent contractions of aorta segments at 37°C and 24°C. The maximum response and pD2 values were reduced by PVAT in both sexes at 37°C. The reduction in pD2 value was significantly greater in aorta segments from female rats. Cooling (24 °C) reduced the maximum response but not pD2 values to PE in aorta segments without PVAT in both sexes. The anti‐contractile effect of cooling was attenuated in the presence of PVAT. Apocynin (3×10−4M) equipotently inhibited PE‐induced contractions both temperatures. L‐NAME (10−4M) potentiated PE‐induced contractions more in aorta segments without PVAT at both temperatures. The expression of eNOS protein and basal level of nitric oxide (NO) were greater in aorta segments with PVAT at both temperatures. However, PE significantly increased levels of NO only in aorta segments without PVAT. We concluded that PVAT attenuated the anti‐contractile effect of cooling by reducing generation of NO.Support or Funding InformationSupported by the College of Graduate Studies and a grant (MR 05/15) from Kuwait University Research Sector.
Vascular Endothelial Over‐Expression of Human Soluble Epoxide Hydrolase (Tie2‐sEH Tr) Attenuates Coronary Reactive Hyperemia in Mice: Role of Oxylipins and ω‐Hydroxylases
Authors: Hanif Ahmad , Edin Matthew L , Zeldin Darryl C , Morisseau Christophe , Falck John R , Nayeem Mohammed A 
Published: November 2023

Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins with opposing biologic effects: epoxyeicosatrienoic acids (EETs) and omega‐(ω)‐terminal hydroxyeicosatetraenoic acids (HETEs). EETs have numerous beneficial physiological effects, including vasodilation and protection against ischemia/reperfusion injury, whereas ω‐terminal HETEs induce vasoconstriction and vascular dysfunction. We evaluated the effect of these oxylipins on post‐ischemic vasodilation known as coronary reactive hyperemia (CRH). CRH prevents the potential harm associated with transient ischemia. The beneficial effects of EETs are reduced after their hydrolysis to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). ω‐terminal HETEs are formed by ω‐hydroxylase family members. The relationship among endothelial over‐expression of sEH (Tie2‐sEH Tr), the changes in oxylipins it may produce, the pharmacologic inhibition of ω‐hydroxylases, activation of PPARγ, and CRH response to a brief ischemia is not known. We hypothesized that CRH is attenuated in isolated mouse hearts with endothelial sEH over‐expression through modulation of oxylipin profiles, whereas both inhibition of ω‐hydroxylases and activation of PPARγ enhance CRH. Compared to WT mice, Tie2‐sEH Tr mice had decreased CRH, including repayment volume, repayment duration, and repayment/debt ratio (P < 0.05), whereas inhibition of ω‐hydroxylases increased these same CRH parameters in Tie2‐sEH Tr mice. Inhibition of sEH with t‐AUCB reversed the decreased CRH in Tie2‐sEH Tr mice. Endothelial over‐expression of sEH significantly changed oxylipin profiles, including decreases in DHETs, mid‐chain HETEs, and prostaglandins (P < 0.05). Treatment with rosiglitazone, PPARγ‐agonist, enhanced CRH (P < 0.05) in both Tie2‐sEH Tr and wild type (WT) mice. These data demonstrate that endothelial over‐expression of sEH (through changing the oxylipin profiles) attenuates CRH, whereas inhibition of ω‐hydroxylases and activation of PPARγ enhance it.Support or Funding InformationThis work was supported by National Institutes of Health (HL‐114559) to M. A. Nayeem, and the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES025034 to D. C. Zeldin).
Microscopic Topography of Atrioventricular Conduction System–A Feature of Potential Clinical Significance
Authors: Sahni Daisy , Randhawa Arpan , Gupta Tulika , Aggarwal Anjali 
Published: November 2023

ObjectivesProximity of atrioventricular (AV) conduction system to tricuspid, mitral and aortic valves renders it susceptible to injury leading to disturbances in patients undergoing valve operations and radiofrequency catheter ablations. Hence, the knowledge of topography of AV conduction system and its relations with surrounding cardiac structures is indispensible.MethodsIn 20 cases, a tissue block of 3×4 cm at AV septal junction was excised which included the borders of Koch's triangle. The block was divided into three equal segments by parallel vertical incisions made perpendicular to insertion of septal leaflet of tricuspid valve. Each segment was processed for Hematoxylin & Eosin and Gomori stain.ResultsThe upper pole of compact AV node was at the level of mitral valve leaflet in 50% cases. Lower pole of AV node was vertically above tricuspid septal leaflet and at the level of muscular IV septum in 100% and 66.7% cases respectively. The subendocardial depth of upper and lower pole of AV node was 1.45±0.6 mm and 0.92±0.3 mm respectively. Minimum subendocardial depth (0.68±0.2mm) was seen at the center of compact AV node. Penetrating bundle of His was seen at the level of tricuspid septal leaflet just deep to it, while Branching bundle of His was 1.98±1.5 mm below the tricuspid septal leaflet. AV nodal extensions began at the level of mitral valve leaflet while its inferior extension ended 2.92±1.3 mm above tricuspid septal leaflet.ConclusionPrior knowledge of distances of AV conduction system from the surrounding landmarks might help in surgical incision planning, safe suture placement and successful device insertion.Support or Funding InformationFrom Director PGIMER, Chandigarh, India.
Modification of CUL3 by Related to Ubiquitin (RUB) is partially regulated by the Phytochrome B pathway in Arabidopsis thaliana.
Authors: Orellana Aaron , Christians Matthew 
Published: November 2023

Plant growth and development depends on detecting the different wavelengths in the electromagnetic spectrum in order to perceive light conditions and grow accordingly. Phytochrome B, a red and far‐red light photoreceptor in plants, plays an integral role in shade avoidance, flowering time, seed germination, and de‐etiolation. Proper degradation of this photoreceptor and the immediate downstream signaling components, the Phytochrome Interacting Factors (PIFs), is crucial to the function of these processes and occurs via the ubiquitin‐proteasome system. The Light Regulating Bric‐a‐Brac/Tramtrack/Broad Complex proteins (LRB1 and LRB2) interact with CUL3 to form an E3 ligase complex which facilitates the attachment of ubiquitin to phytochrome B and PIF proteins. In plants, cullin‐based E3 ligase activity is dependent on the attachment of RUB (the plant ortholog of NEDD8 in human and other species) to cullin. We found that the LRB proteins contain two highly conserved regions near the N‐terminus which are similar to regions on CUL1/2 and RBX1, and these regions may play a role in the Rubylation process. Further investigation determined that the levels of Rub‐modified CUL3 are modulated by red light, and the PhyB signaling pathway plays a role in this process. To determine if the N‐terminal region of the LRBs play a role in rubylation of CUL3, a truncated version of the LRB gene missing this highly conserved region was inserted into wild type and a lrb1 lrb2 double mutant in Arabidopsis thaliana. Phenotypic, genetic, and immunoblot analysis of homozygous lines featuring the truncated LRBs suggest that the N‐terminal region may affect the ability of the LRBs to regulate red light responses. Future analysis of this region will provide insight into its role in phytochrome degradation and rubylation of CUL3.Support or Funding InformationThis research is funded by an S3 Summer Scholars Grant through the Office of Undergraduate Research at Grand Valley State University
Characterizing small molecule inhibitors of the LINE1 endonuclease
Authors: Smith Michaela , Bertrand Sarah , Bolden Quinteshea , Russell Brittany , DeFreece Cecily 
Published: November 2023

Our lab studies the mammalian mobile long interspersed element 1 (LINE1). LINE1 elements mobilize in the genome through a copy and paste itself into new genomic loci through the process of retrotransposition. The full‐length LINE1 element is comprised of two open reading frames, ORF‐1 and ORF‐2. The latter protein, ORF‐2, encodes an endonuclease, which is responsible for nicking DNA near the adenine‐thymine rich base sequence. Proper functioning of LINE1 endonuclease facilitates the mobilization of the element and requires the formation of DNA damage in the form of double‐strand breaks (DSBs), which could, in turn, lead to diseases such as cancer. Approximately eighteen percent of the human genome is comprised of the LINE1 sequence and the expression of LINE1 proteins and mobilization of the LINE1 element has been implicated in several cancers, such as breast and prostate cancers. While events of LINE1 insertion may be mutagenic, the effect of the LINE1 endonuclease on genetic instability is unclear. If the DNA DSBs associated with LINE1 endonuclease are not repaired faithfully, then mutations may result that lead to disease onset or progression. In our laboratory we have identified small molecule inhibitors of the LINE1 endonuclease. Here we present our work investigating the impact of the small molecule inhibitors on the formation of LINE1 endonuclease associated DNA DSBs.Support or Funding InformationThe work presented is supported in part by monies from P20GM103424, TL4GM118968 and 5RL5GM118966‐03 as well as the Louisiana Cancer Research Consortium. We also thank the Molecular and Cellular Biology core at Xavier University of Louisiana.
Antioxidant effects of Agastache mexicana extracts: an in vitro approach
Authors: Esquivel‐Gutiérrez Edgar R. , Coria‐Orozco Emilio , Torres‐Martínez Rafael , Hernández‐García Alejandra , Ríos‐Chávez Patricia , Manzo‐Ávalos Salvador , Saavedra‐Molina Alfredo , Salgado‐Garciglia Rafael 
Published: November 2023

Agastache mexicana (Kunth) Lint & Epling (toronjil) is a medicinal plant distributed in the Michoacan state in Mexico and used in traditional medicine for gastrointestinal disorders, anxiety, cardiovascular alterations and efficiently as an anti‐inflammatory and analgesic among others. Ethnobotanical, pharmacological and phytochemical studies have been carry out, however there are currently no scientific relevance studies that support their therapeutic properties. Toronjil have mainly volatile oils (camphene, β‐pinene, limonene, 1,8‐cineole, furfural, citronellal, menthol and pulegone) into their chemical composition, all of them knows as antioxidants. Notwithstanding, there are not reports about the effects of toronjil over the oxidative stress, either in vivo and/or in vitro assays. By this reason, the main aim of this work is to evaluate in vitro the antioxidant properties of Agastache mexicana and some of their isolated compounds. Hydroalcoholic, methanolic and hexanic (Soxhlet) extracts were obtained from toronjil aerial parts and different concentrations (0.001, 0.01, 0.1 and 1 mg ml−1) were tested using the DPPH, ABTS and TBARS methods to evaluate the antioxidant capacity. Our results indicated that the methanol extract (since the 0.1 mg ml−1) has the capacity to scavenger or inhibit the free radicals tested with any assay mentioned here (DPPH, ~93%; ABTS, ~99% and TBARS, ~94%); our GC‐MS analysis reveals the presence of limonene, linalool, mentone, α‐terpineol, pulegone and eugenol mainly. Only eugenol is a potent scavenger of free radicals because its remove ~94%, ~98% and ~98% using the DPPH, ABTS and TBARS methods respectively. The rest of the compounds tested have a relatively low capacity to remove free radicals by either method assayed.In conclusion, methanolic extract from Agastache mexicana, is a candidate to carry out an “in vivo” approach using an animal model that reflects high oxidative stress.This work was supported by CIC‐UMSNH/2016‐2017 RSG.Support or Funding InformationThis work was supported by CIC‐UMSNH/2016‐2017 to RSG. CIC‐UMSNH 2.16 to ASM.
Effects of the Vascular Disrupting Agent OXi8006 on Activated Endothelial Cell Signaling and Tumor Growth Delay in a Breast Cancer Mouse Model Treated with the Corresponding Phosphate Prodrug Salt OXi8007
Authors: Odutola Samuel O. , Strecker Tracy E. , Taylor Emily A. , Schwartze Jeffrey , Gerberich Jeni , MacDonough Matthew T. , Chaplin David J. , Liu Li , Mason Ralph P. , Pinney Kevin G. , Trawick Mary Lynn 
Published: November 2023

Tubulin‐binding, small‐molecule vascular disrupting agents (VDAs) are anticancer agents that rapidly depolymerize microtubules in the activated, tumor endothelium causing a pronounced shutdown in blood flow while leaving normal tissues intact. VDAs offer significant therapeutic advantage against solid tumors by selectively targeting pre‐established tumor vasculature and are mechanistically distinct from antiangiogenic agents. The indole‐based tubulin‐binding compound OXi8006 and its phosphate prodrug OXi8007 have shown promise as VDAs although important questions regarding features of their mechanism of action remain. We have shown that OXi8006 and OXi8007 disrupted microtubules in activated human umbilical vein endothelial cells (HUVECs) and caused extensive reorganization of the cytoskeletal network. The pathway involved an increase in phosphorylation of non‐muscle myosin light chain and focal adhesion kinase, resulting in increased actin stress fiber and focal adhesion formation via the intramolecular G protein switch RhoA and RhoA dependent kinase (ROCK) [Strecker et al. Cancer Lett. 369, 229 (2015)].An important unresolved question is the connection between microtubule disruption and the downstream effects of VDA treatment. In this study we demonstrated the role of GEF‐H1, a protein that is able to activate RhoA but is inactive when bound to microtubules. GEF‐H1 is released upon microtubule disruption and can activate RhoA. The downstream effects of RhoA activation upon OXi8006 treatment were abrogated by siRNA‐mediated knockdown of GEF‐H1. We also showed the importance of activation of the LIM kinase/cofilin pathway in actin stress fiber formation with VDA treatment. LIM kinase is phosphorylated and activated by RhoA kinase and resulted in phosphorylation of cofilin, thus inhibiting the ability of cofilin to disassemble actin filaments. Treatment of HUVECs with LIM kinase inhibitor significantly diminished the actin stress fiber formation observed with OXi8006 treatment alone. In MDA‐MB‐231 breast cancer cells, OXi8006 treatment reduced cell migration. The water soluble prodrug OXi8007 caused significant tumor growth delay in an MDA‐MB‐231 breast cancer xenograft mouse model. The results of this study elucidated important aspects of the mechanism of tubulin‐binding VDA action, and confirmed the potent anticancer effects of the VDA prodrug OXi8007.
Differential Sedimentation of Linear versus Circular DNAs Using Divalent Metal Cations
Authors: England Corbin James , Grey Tanner , Lewis Kevin 
Published: November 2023

Molecular biologists routinely purify and concentrate DNA and RNA molecules by precipitation with ethanol, a method that does not discriminate between the different structural forms of each nucleic acid. In the current project we have assessed the ability of monovalent Group I and divalent Group II metal cations to selectively precipitate DNAs with different shapes and sizes out of aqueous solutions. Particular emphasis was placed on separation of circular plasmid DNAs from contaminating linear chromosomal DNA fragments. This was done by mixing Group 1 or Group 2 metals with DNA at various pH values then spinning the solutions in a microcentrifuge. The absorbance was then measured at 260 nm. Group 1 metal ions proved to be ineffective at sedimenting large chromosomal DNA fragments. Group 2 metal cations (Mg2+, Ca2+, Sr2+ and Ba2+) sedimented linear DNAs strongly, but only at high pH values (10–12). Ca2+ was chosen for further experiments because it is not a cofactor for nucleases like Mg2+ and it is found naturally within cells, unlike Sr2+ and Ba2+. Preliminary studies involving manipulation of parameters such as metal and buffer concentrations identified conditions that allowed chromosomal DNA to be sedimented approximately 10 times more efficiently than supercoiled plasmid DNA. Current experiments are seeking to maximize this difference in precipitation efficiencies, with a focus on sedimenting linear chromosomal DNA while leaving supercoiled plasmid DNA in solution.Support or Funding InformationTexas State University
Online Learning Modules Based on Spacing and Testing Effects Improve Medical Student Performance on Anatomy Examinations
Authors: Baatar Dolgor , Ricks Elizabeth , Gest Thomas 
Published: November 2023

Recent studies demonstrated that spaced education enhances learning in various educational settings. However, the efficacy of spaced education for learning anatomy remains unknown. Spaced education is based on two main findings of the cognitive research: spacing effect (knowledge retains better when acquired in small pieces at spaced intervals) and testing effect (repeated testing improves knowledge retention). The aim of this study was to determine whether the use of a spaced education online learning tool improves medical student performance on written anatomy examinations.The online educational platform Cerego (http://cerego.com) was used to create a learning module (set) on the anatomy of the head and neck which is one of the most challenging topics for students as judged by low performance on related examination questions. One hundred and six first‐year medical students were provided with a set one week before the corresponding anatomy laboratory session. The Cerego platform allows assigning various goal levels for each set. Progress to the goal (0–100%) is measured by the frequency of use and the accuracy of responses to quiz questions. For this set, the goal level was set to 1 (achievable in one week). The relationship between the set usage data and the anatomy examination scores was analyzed. Student perceptions of the set were assessed through a survey.More than half of the Class (59 students) have used the set. Based on the percent of progress to the goal, the users were designated as High Users (19 students who had 50% or more progress to the goal) and Low Users (40 students who had less than 50% progress to the goal). Students who did not use the set were designated as Non‐Users (n=47). The student anatomy rank (average score of anatomy questions from 3 previous summative examinations) was not significantly different between the 3 groups. High Users performed significantly better than Non‐Users on anatomy examination questions related to the material included in the set. Performance on anatomy questions unrelated to the set (Control items) was not different between the groups. Set use was associated with improved overall anatomy grades of students who fell into the bottom half of the Class by the anatomy rank. Surveys have shown that the majority of students found Cerego sets useful and effective. Lack of time was reported as the most common barrier to using the set.This study shows that the use of online anatomy learning tools which utilize spacing and testing effects is associated with improved medical student performance on anatomy examinations. These results support the increased use of such learning tools as an adjunct to anatomy instruction in medical schools.
Using Metabolite Profiling to Understand the Consequences of Iron‐Source Choices by Staphylococcus aureus
Authors: DuBois Jennifer , Celis Arianna 
Published: November 2023

Bacteria inhabiting different environments are presented with different sources of nutritional iron. Major metabolic decisions are often made based on what sources of iron are available, and how limited those sources might be. For Staphylococcus aureus, heme iron is preferred under pathogenic conditions, where the bacteria survive by lysing red blood cells and consuming hemoglobin. We therefore hypothesize that Staphylococcus aureus may regulate a whole variety of metabolic decisions based on the sensed availability of heme. To test this hypothesis and examine the fate of heme and non‐heme iron sources, we are using NMR‐ and mass spectrometric based methods to show how whole‐cell metabolite pools change in response to changes in iron sources. Results from initial studies will be presented.Support or Funding InformationNIH R01 GM‐090260