bluuebunny/crossref_metadata_2025_split huggingface dataset:
Searching for a New Anti‐Cancer Drug: Investigation of KY Hemp‐Induced Apoptosis in Ovarian Cancer Cells
Authors: Sumanasekera Wasana K. , Johnson Christina , Pham Anh‐Thoa , Patel Brijesh , Sivamohan Anjali , Cox Art 
Published: June 2021

Marijuana (cannabis sativa) is a schedule 1 drug that has been recently approved by some states in the US for its therapeutic benefit. Although there are a few reports about its anti‐cancer potential, currently it has been used mainly for treatment‐resistant epilepsy and to alleviate pain. However, marijuana is addictive and causes mind‐altering actions. Hemp, which belongs to the same genus and species as marijuana, shows similar therapeutic benefits without addictive potential. Our laboratory is interested in examining for unconventional therapies for ovarian cancer. The main objective of the current study is to investigate hemp‐induced modulation of A2780 ovarian cancer cell apoptosis.MethodsKY‐Hemp extracts were made via supercritical CO2 extraction, and its cannabidiol content was analyzed using HPLC by KY commonwealth Extracts and MRX laboratories respectively. In our laboratory this hemp extract, which contained cannabidiol (CBD) and minimal tetrahydrocannabinol (THC) was tested for its anti‐cancer effects. A2780 epithelial ovarian cancer cells (OCCs) were seeded in 12‐well plates. Following serum starvation, the OCCs were treated with vehicle (no hemp negative control), Staurosporine (positive control for apoptosis) or different concentrations of hemp extracts for 24 hours. Then cell supernatants were removed and subject to Bradford protein assay followed by caspase‐3 ELISA. Caspase‐3 is one of the major caspases released from apoptotic cells. Caspase‐3 released from each treatment group was detected using caspase‐3 ELISA based on manufacturer's protocol. In brief, caspase‐3 standards and cell supernatants from all treatment groups, including negative and positive controls, were incubated in ELISA plates coated with caspase‐3 antibodies. After a series of steps that included treatment with secondary antibodies and a substrate solution, caspase‐3 levels were detected spectrophotometrically. To ensure the reproducibility, each experiment was repeated a minimum of three times. We also studied pure CBD (analytical standard from Sigma Aldrich) induced apoptosis in A2780 OCCs. Our results indicate that KY hemp extract cause significant increase in caspase‐3 release, which is indicative of apoptosis of OCCs. Caspase‐3 release is significant at hemp extracts that contain 83.5 μM and 167 μM CBD. KY hemp‐induced caspase‐3 secretion is somewhat comparable to pure CBD‐induced caspase‐3 release. Currently we are investigating the anti‐apoptotic effects of hemp at lower concentrations. Based on the data here we conclude that KY hemp has anti‐cancer potential against ovarian cancerSupport or Funding InformationFunding was provided by Sullivan University System via a faculty development grant awarded to Dr. SumanasekeraThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Epstein Barr virus and Multiple Sclerosis
Authors: Rodriguez‐Pérez Jose Alejandro , Pérez‐Vallín Vanessa , Mirabal‐Viel Alejandro , Padrón‐González Alexander Ariel , Castillo‐González William , González‐Losada Cristobal , Dorta‐Contreras Alberto Juan 
Published: June 2021

Cause of Multiple Sclerosis is not well known yet. There are theories that oint out a viral origen that may initiate the autoimmune response. There are a lot of biological agents that could be causative. Among them is Epstein Barr Virus but there are controversies about this topic. With the evaluation of the specific antibody index developed by Reiber, perhaps it will be possible to find some evidences that sign Epstein Barr virus like the cause of the disease. The aim of this paper is to evaluate the antibody index anti‐Epstein Barr virus in 27 patients with multiple sclerosis and 19 control cases. There were significant differences between Qspecific (Specific antibodies in CSF/Specific antibodies in serum) between the sclerosis multiple group and the control group (p<0.0001). The antibody index( Qspecific/Q IgG or Q lim) between both groups was not significant differences (p=0.0519). Anti‐Epstein Barr Qspecific in Multiple Sclerosis could contribute to clarify the etiology of this disease but it is necessary to increase the total of patients involved in the sample in order to confirm that the antibody index in patients could be definitively a probe of Epstein Barr virus as the causative of the disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Furosemide Reduces BK‐αβ4‐Mediated K+ Secretion in Mice on an Alkaline High K Diet
Authors: Wang Bangchen , Sansom Steven 
Published: June 2021

Because of its cardio‐protective benefits, a high K diet is often warranted in conjunction with diuretics such as furosemide for treating hypertension. It is critical to understand how such diets influence the diuretic actions on renal K handling in order to choose the best drug for patients. Studies have shown that furosemide acidifies the urine by increasing acid secretion from thick ascending limb. On the other hand, the Ca2+‐activated large conductance K channel (BK‐αβ4) is regulated by pH. We hypothesized that in mice on an alkaline high K diet (HK), furosemide reduces BK‐αβ4‐mediated K+ secretion in the distal nephron by acidifying the urine. To test our hypothesis, HK‐adapted wild‐type (WT) and BK‐β4 knockout mice (β4KO) were given either control water or furosemide water (0.1 g/L). Urine was collected in metabolic cages on the day before treatment and 1, 4, 7, 11, and 14 days after treatment. Mice were then sacrificed to collect blood and kidneys. The urine pH was reduced after furosemide treatment in both WT and β4KO. Urinary K+ excretion was reduced on day 1 of furosemide treatment in WT (2801 ± 235 vs. 2175 ± 119 μmol/day) but not β4KO (1934 ± 497 vs. 2395 ± 207 μmol/day). After 14 days of treatment, renal K+ clearance was decreased and plasma [K+] increased in WT (ctrl water: 591 ± 45 mL/day; 4.46 ± 0.13 mM vs. furo water: 424 ± 32 mL/day; 5.13 ± 0.10 mM) but not β4KO (ctrl water: 453 ± 42 mL/day; 5.04 ± 0.19 vs. furo water: 516 ± 64 mL/day; 5.03 ± 0.06 mM). Additionally, renal K+ clearance was positively correlated with urine pH in WT but not β4KO. Western blotting and immunofluorescence staining showed that furosemide decreased total protein expression of BK‐β4 and reduced apical localization of BK‐α. These results indicate that in mice on HK, furosemide reduced BK‐αβ4‐mediated K+ secretion by acidifying the urine, making furosemide a K‐sparing diuretic in the setting of an alkaline high K diet.Support or Funding InformationThis project was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants R01‐DK‐092474, R01‐DK‐071014 and F30‐DK‐108456.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CHIP regulates Aquaporin‐2 Quality Control and Body Water Homeostasis
Authors: Wu Qi , Moeller Hanne B. , Stevens Donté A. , Sanchez‐Hodge Rebekah , Childers Gabrielle , Kortenoeven Marleen L.A. , Cheng Lei , Rosenbaek Lena L. , Rubel Carrie , Patterson Cam , Pisitkun Trairak , Schisler Jonathan C. , Fenton Robert A. 
Published: June 2021

The importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) are highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins play a regulatory role in these cells and how these cells can be regulated by individual physiological stimuli. By combining proteomics, bioinformatics, and cell biology approaches alongside gene targeted animal models, we found an essential role of the E3 ubiquitin ligase CHIP for modulating the abundance of the water channel aquaporin‐2 (AQP2). CHIP is highly expressed throughout the collecting duct, modulated in abundance by vasopressin, interacts with AQP2, Hsp70 and Hsc70 and can directly ubiquitylate AQP2 in vitro. shRNA knockdown of CHIP in CCD cells increased AQP2 protein half‐life and reduced AQP2 ubiquitylation, resulting in greater AQP2 and phosphorylated AQP2 levels. Plasma membrane abundance of AQP2 was increased in CHIP knockdown cells. CHIP knockout mice or novel CRISPR/Cas9 mice without CHIP E3 ligase activity had greater AQP2 abundance and altered renal water handling, with decreased water intake and urine volume, alongside higher urine osmolality. No significant changes in other water or sodium transporting proteins were observed in the gene‐modified mice. In summary, CHIP has a regulatory role for AQP2 and subsequently renal water handling.Support or Funding InformationQ.W. is supported by European Union Horizon 2020 Marie Skłodowska‐Curie Individual Fellowship project 705682, Danish Medical Research Council grant 6110‐00118B, and Lundbeck Foundation grant R192‐2015‐804. M.L.A.K. is supported by Danish Medical Research Council grant 1333‐00279. Funding is provided by National Institutes of Health grant R37 HL065619 (to C.P. and J.C.S.). Funding is also provided by the Novo Nordisk Foundation (R.A.F.), the Lundbeck Foundation (R.A.F.), and the Danish Medical Research Council (R.A.F.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of the Occluding Septate Junction Protein Mesh in Epithelial Integrity and Ion Transport in the Drosophila Renal Tubules
Authors: Jonusaite Sima , Rodan Aylin 
Published: June 2021

Background/objectiveEpithelial occluding junctions are specialized cell‐cell junctions that establish and maintain cell polarity and control paracellular ion, solute and water transport. Tight junctions are the occluding junctions in the epithelia of vertebrates, whereas the epithelia of invertebrates possess septate junctions (SJs). Molecular and genetic analysis of Drosophila SJs have identified a number of transmembrane as well as cytoplasmic scaffolding proteins expressed in a tissue‐specific manner. However, many questions about the role of these proteins in SJ assembly, maintenance and function remain open. Recently, an integral protein, Mesh, has been identified within the SJs of Drosophila midgut and renal tubule epithelia, and shown to be required for the barrier function of the midgut. Here, we report, for the first time, examination of the role of Mesh in adult fly renal tubules, whose function in the maintenance of internal homeostasis relies on regulated transepithelial ion and water secretion/absorption.Methodsmesh knockdown in the fly tubules was achieved using the GAL4‐UAS system. Expression and localization of Mesh and a scaffolding SJ protein, Discs large (Dlg), in control and mutant tubules were determined using confocal microscopy and available antibodies. Transepithelial fluid and K+ transport in the main segment of the control and mesh knockdown tubules were measured using the Ramsay assay and a K+‐specific electrode.ResultsAdult fly renal tubules consist of four major morphologically and functionally distinct segments and have two cell types, the larger principal cells and smaller intercalated stellate cells. We found that developmental mesh knockdown in the tubule principal cells was associated with enlarged initial and main segments of the adult fly tubule and reduced septate junctional localization of a scaffolding protein, Dlg, especially in the enlarged initial segment. In addition, the main segment transepithelial fluid and K+ transport in isotonic condition was abolished in mesh knockdown tubules compared to the control groups.Conclusions and significanceThese data suggest that the SJ protein Mesh is required for SJ assembly, epithelial integrity and ion transport in the fly renal tubule epithelium. Since the Mesh mammalian homolog, Susd2, is also highly expressed in the mouse renal epithelium with unknown function, these studies pave the way for further characterization of the Mesh/Susd2 family of proteins in both invertebrates and vertebrates.Support or Funding InformationThis project was supported by NIH/NIDDK to ARRThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identifying the Location of the Foramen Ovale via the Articular Eminences, Molars, and Occipital Condyles
Authors: Daubenspeck Madison R. , Zdilla Matthew J. 
Published: June 2021

The foramen ovale of the sphenoid bone is often cannulated for the treatment of trigeminal neuralgia. The success of foramen ovale cannulation procedures depends upon the properly locating the foramen, most often via fluoroscopy. Miscannulation may result in severe adverse events including intracranial hemorrhage and death. Unfortunately, despite fluoroscopic guidance, miscannulations continue to occur. Therefore, study of the location of the foramen ovale relative to anatomical landmarks that are easily identifiable through fluoroscopy is warranted. This study assessed the location of the foramen ovale in 228 crania. Three lines drawn upon digital photographs were assessed with regard to whether or not they traversed the foramen ovale. The lines included 1) a sagittal line drawn through the posterior‐most molar; 2) a line drawn through both the posterior‐most molar and the lateral‐most aspect of the ipsilateral occipital condyle; and 3) a transverse line drawn between the articular eminences. Of all the lines, the transverse line most consistently traversed the foramen ovale, bilaterally (left side: 159:228, 69.7%; right side: 157:228, 68.9%; bilateral: 316:456, 69.3%). Likewise, sagittal lines traversed the foramen more often than not. Because the articular eminence is easily identifiable via fluoroscopy from a lateral projection, the results of this study suggest that the articular eminence, in particular, may be a useful landmark for the cannulation of the foramen ovale. Moreover, using the articular eminence in conjunction with the molars and occipital condyles may improve localization of the foramen ovale from both lateral and AP views.Support or Funding InformationWV Research Challenge Fund [HEPC.dsr.17.06] and [HEPC.dsr.14.13]This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Three‐Dimensional Infraorbital Foramen Location Relative to Facial Landmarks: Preliminary Results
Authors: Hartnell Lauren E. , Koons Aaron W. , Lynch Hannah L. , Ganoe Maria R. , Lambert H Wayne , Zdilla Matthew J. 
Published: June 2021

Infraorbital nerve block injections are performed by either an intraoral approach per the oral vestibule or an extraoral approach through the skin near the infraorbital foramen. Many studies have assessed the location of the IOF relative to bony landmarks, teeth, as well as soft tissue landmarks with mixed results. Few studies have assessed the location of the IOF in three dimensions. This study analyzed the location of the IOF relative to a midpoint between the inferolateral nasal aperture and inferolateral orbital rim via three‐dimensional models rendered from 18 adult crania. The distance from the midpoint to the IOF averaged 4.16±1.43 mm (mean±SD) on the left and 3.93±1.43 mm on the right. Wilcoxon matched‐pairs signed rank tests revealed no significant difference among sides (p=0.325). This report also addresses differences among the x, y, and z axes. These preliminary data demonstrate the utility of three‐dimensional analysis for the assessment of IOF location. Understanding the location of the IOF in three dimensions may aid in determining the best patient‐specific approach for infraorbital nerve block.Support or Funding InformationWV Research Challenge Fund [HEPC.dsr.17.06] and [HEPC.dsr.14.13]This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Relationship of the Articular Eminence with the Mandibular Fossa: Implications for Temporomandibular Joint Mechanics
Authors: Bodnar Sarah E. , Zdilla Matthew J. 
Published: June 2021

The temporomandibular joint varies from most joints in that it is ginglymoarthrodial, both a hinge and a gliding joint. Early opening of the mouth produces a rotational movement at the joint; however, with wide mouth opening, the mandibular condyle translates anteriorly beyond the articular eminence. In some circumstances, the translation of the mandibular condyle over the articular eminence produces a dislocation of the mandible with concomitant spasm of local musculature, thereby holding the mandible in an open position. In certain circumstances, conservative treatments may prevent future dislocations. However, occasionally, surgeries such as eminectomy may be warranted. Because of the aforementioned relationship of the articular eminence with the movement of the mandible, the anatomy of the articular eminence warrants study in order to attain a better understanding of the temporomandibular joint mechanics. Therefore, this study assessed the angle formed by the anterior and posterior boundaries of the articular eminence and the angle formed between the posterior border of the mandibular fossa with the anterior border of the mandibular fossa (i.e., the posterior border of the articular eminence)—angles A and B, respectively. A total of 102 left sides and 99 right sides were analyzed. The average angle A was 112.5±14.49° (Mean±SD) and the average angle B was 112.4±13.28°. Angles A and B were correlated (r=0.41; p<0.0001). Paired t‐tests revealed no statistically significant difference between angle A, bilaterally (t=1.543(80); p=0.1268). However, there was a statistically significant difference between left‐ and right‐sided angle B (t=4.045(77); p=0.0001). The results of this study suggest that there is bilateral asymmetry among mandibular fossae. Similarly, the anterior and posterior boundaries of the articular eminence do not differ significantly from side‐to‐side. Further study should incorporate the size of the articular eminence and mandibular fossa in relation to the angular data presented here.Support or Funding InformationWV Research Challenge Fund [HEPC.dsr.17.06] and [HEPC.dsr.14.13]This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fibrosis And Scarring of The Brachial And Sacral Plexus as Displayed by MRI/MRA/MRV
Authors: Collins James D. , Saxton Ernestina Howell , Gelabert Hugh Anthony , Carnes Alfred 
Published: June 2021

Bilateral rounding of the shoulders (laxity) associated with kyphosis of the thoracic spine causes costoclavicular compression and brachial plexopathy. This form of thoracic outlet syndrome is usually not amenable to surgical treatment in older patients, particularly in severe kyphosis of the thoracic spine. Surgery alters fascial planes within the thorax and pelvis that causes fibrosis and scarring of the blood supply to the brachial and sacral plexus. The objective of this presentation is to display the sites of landmark anatomy compressing the brachial plexus that decreases venous return supply to the nerves causing a shortage of oxygen and glucose needed for cellular metabolism causing fibrosis and scarring of the soft tissues marginating the brachial and sacral plexus. Magnetic Resonance Imaging (MRI) is the only modality that displays fibrosis and scarring of fascial plane anatomy obstructing venous and lymphatic return not possible with ultrasound or Computerized Axial Tomography (CAT). The longer venous obstruction transient ischemia or permanent obstruction ischemia if unrelieved, progressively affect the nerve fibers increasing numbers to an increasing degree. Pathology develops with edematous swelling and vascular congestion. If the pressure is unrelieved and continues to increase, the nerve(s) suffer a first degree or a conduction block injury. Compression ischemia with degeneration and fibrosis develop. In absence of relief, the endoneurial tubes and funniculi atrophy increasing ischemia, fibrosis becomes marked. This presentation displays costoclavicular compression of the brachial and sacral plexus with fibrosis and scarring in two patients. One patient post multiple fractures of the thorax and pelvis complicated by thoracic outlet syndrome post pelvic hardware, and the second patient post cervical fusion and bilateral total shoulder and hip replacement with foot drop. Monitored bilateral MRI, MRA and MRV of the brachial plexus is the only modality of choice to display costoclavicular compression and fibrosis, and scarring of the brachial plexus.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of MEK1/2 and MEK5 Pathway Disruption on Skeletal Phenotypes in Intact Female SCID Mice
Authors: Peacock Sarah J. , Middleton Kevin M. , Cavanaugh Jane , Wright Thomas , Burow Matthew , Barnes Van , Munmun Fahima , Witt‐Enderby Paula 
Published: June 2021

Many receptor‐mediated cellular processes progress through mitogen‐activated protein kinase (MAPK) signaling pathways, which are initiated by activation of a surface receptor and ultimately lead to a change in cell physiology. Previous research has shown that the influence of melatonin on osteoblast activity is mediated in part through MAPK/ERK kinases (MEK) 1/2 and MEK5. Here we explore the possible effects of MEK 1/2 and MEK5 disruption on the skeletal structure in rodents with diurnal melatonin rhythms. To investigate the influence of MAPK signaling on bone mineral density and trabecular bone phenotypes, one group of SCID mice (SC; n = 4) was injected daily for a period of 30 days with a dual MEK1/2 and MEK5 inhibitor, SC‐1‐151. A second control group (n = 4) was injected daily with DMSO vehicle for the same period. At the end of the experimental period mice were euthanized, and tibiae were dissected free of soft tissues and fixed in formalin. Tibia were scanned at 9.61 μm3 voxel size for subsequent morphometric analyses. Regions of interest were identified on the scans and then analyzed for trabecular thickness (Tb.Th), trabecular spacing (Tb.Sp), bone volume fraction (BV/TV), and cortical bone mineral density (BMD) using ImageJ software. Resulting bone phenotypes were analyzed using Bayesian linear models. We found that the SC group showed credibly decreased BV/TV compared to the DMSO controls (Pr[SC < DMSO] = 0.83). However, comparisons of Tb.Th, Tb.Sp, and BMD indicated minimal credible differences between the SC and DMSO treatment groups. Overall, our results suggest that, while previous research has shown that disruption of the MAPK signaling pathway may have a negative effect on osteoblast activity, these effects may result in only subtle changes for trabecular bone phenotypes and no change in cortical bone mineralization. This project provides preliminary results for a larger‐scale project investigating the role of melatonin, MEK1/2, and MEK5 in bone formation.Support or Funding InformationResearch support: University of Missouri School of Medicine, National Institute of Arthritis and Musculoskeletal and Skin DiseasesThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.