bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Non‐Polyamine based Polyamine Transport Inhibitors for the Treatment of Pancreatic Ductal Adenocarcinoma
Authors: Moots Holly , Phanstiel Otto 
Published: June 2021

The native polyamines (putrescine, spermidine and spermine) are low molecular weight, biogenic amines, which play key roles in transcription, translation, immunity and chromatin remodeling. Polyamine depletion results in inhibited cell growth and has been used to treat human cancers with mixed results. While inhibitors of polyamine biosynthesis, like difluoromethylornithine (DFMO), result in intracellular polyamine depletion and decreased cell growth, the effect is mostly cytostatic. Indeed, cancer cells when treated with DFMO often rescue themselves by upregulating polyamine import to replenish their depleted polyamine stores. In this regard, a combination therapy comprised of a polyamine synthesis inhibitor (e.g., DFMO) and a polyamine transport inhibitor (PTI) are required to provide sustained polyamine depletion and limit tumor growth.Our group has previously developed polyamine‐based PTIs and this report describes our efforts to develop non‐polyamine based PTI agents in hopes of improving drug efficacy. These agents are predicated upon piperazine scaffolds and provide an opportunity to develop orally active PTIs to be given in combination with DFMO. The remarkable thing about this technology is that the DFMO+PTI therapy not only inhibits cancer cell growth, but also unleashes the immune system to attack the tumor. In this regard, this approach provides a novel ‘chemoimmunotherapy’ to help patients with cancer. Since pancreatic cancer is the third leading cause of cancer‐related death with few treatment options available, we have developed these new medicines in hopes of providing new approaches to attack these seemingly ‘immunologically‐quiet’ tumors. This report will describe the development of our synthetic efforts to optimize these PTI designs.Support or Funding Information2016 Florida Translational Research Program Award and the 2018 Bankhead Coley Cancer Research Program Award # 8BC05.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Aqueous Gladiolus psittacinus Bulb Extract Influences Antioxidant Enzymes Activities in Diabetic Rats
Authors: Oyetayo Folake Lucy , Oseni Olatunde Abass 
Published: June 2021

Aqueous extract of the bulb of Gladiolus psittascinus a tropical plant used as adjunct in the preparation of a non‐alcoholic drink was evaluated for its antioxidant activities in diabetic albino rats. After a 14‐day acclimatization period, rats were divided into five treatment groups of four animals per group as follows: Group 1: Control (Uninduced), Group 2: Alloxan induced diabetic rats, Group 3: Alloxan induced rats treated with standard drug, Group 4: Un‐induced rats treated 100mg/kg body weight aqueous Gladilous psittascinus bulb extract, Group 5: Alloxan induced diabetic rats treated 100mg/kg body weight aqueous Gladilous psittascinus bulb extract. On the establishment of hyperglycemia, animals were sacrificed; plasma antioxidant enzyme activities and lipid peroxidation levels were estimated. Activities of all antioxidant enzymes evaluated increased significantly. Plasma superoxide dismutase activity significantly increased (p<0.05) in the diabetic untreated rats from13.76±2.50U/L (Group 2) to 45.76±5.40U/L in the diabetic aqueous Gladilous psittascinus bulb extract treated rats (Group 5). Furthermore, Catalase activity in the diabetic group (2.48±0.43U/L) significantly increased (p<0.05) to 10.49±1.98U/L in the diabetic aqueous Gladiolus psittascinus bulb extract treated rats (Group 5) and there was a significant decrease in lipid peroxidation levels in plasma from 13.23±3.14 μmolMDA/L (Group 2) to 6.28±1.05 μmolMDA/L (Group 5). The foregoing shows the potentials of aqueous Gladilous psittascinus bulb extract in enhancing the production of antioxidant enzymes required to scavenge reactive oxygen species produced in the diabetic state. Hence, the Gladilous psittascinus bulb holds promise for the food industry in the control of oxidative changes that may occur during food processing and diet therapy in the management of oxidative stress related disorders such as Diabetes mellitus.Support or Funding InformationTertiary Education Trust Fund (TETFUND) through Ekiti State University Ado‐Ekiti, NigeriaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glycerol Improves Skin Lesions in a Mouse Model of Psoriasis: Possible Mechanism
Authors: Bollag Wendy B , Choudhary Vivek , Uaratanawong Rawipan , Kaddour‐Djebbar Ismail , Custer Victoria , Cohen Elyssa , Zhang Catherine 
Published: June 2021

Psoriasis is a common skin disorder characterized by hyperproliferation and abnormal differentiation of the major cells comprising the skin epidermis, keratinocytes, as well as by skin inflammation. We have previously shown a physical and functional association between the glycerol channel aquaporin‐3 (AQP3) and the enzyme phospholipase D2 (PLD2), which can convert the AQP3‐transported glycerol to phosphatidylglycerol (PG). Further, we have recently demonstrated an ability of PG to inhibit toll‐like receptor‐mediated innate immune system activation by antimicrobial peptides, which are upregulated in psoriasis and can act as danger‐associated molecular patterns to activate toll‐like receptors (TLRs). Glycerol has been reported anecdotally by some patients to improve psoriasis, and we hypothesized that it does so by its PLD2‐mediated conversion to PG. To test this idea, we first demonstrated the ability of topical glycerol to ameliorate inflammation and lesion development in the imiquimod‐induced mouse model of psoriasis. Glycerol reduced ear edema, improved the psoriasis area and severity index (PASI) score, a measure of the appearance and degree of skin lesions, and inhibited the imiquimod‐increased epidermal thickness and tumor necrosis factor‐alpha immunoreactivity. When the same experiment was performed in PLD2 knockout mice, preliminary analysis indicated that glycerol also ameliorated skin lesions; however, topical glycerol is known to function as an emollient, with the capacity to improve skin function and appearance. To overcome this topical glycerol effect, we repeated the experiments using oral glycerol (2% in the drinking water). In the wild‐type mice, oral glycerol again improved the inflammation and skin lesion development induced by imiquimod. On the other hand, there was no significant effect of oral glycerol on these parameters in PLD2 knockout mice. These results provide the first experimental evidence to support the beneficial effects of glycerol in psoriasis. Furthermore, our data suggest that conversion of glycerol to PG underlies in part the glycerol effect and imply that glycerol and/or PG might constitute an effective treatment for this common skin disease.Support or Funding InformationSupported in part by a Research Career Scientist Award and VA Merit Award #CX001357 to WBB. The contents of this article do not represent the official views of the Department of Veterans Affairs or the United States Government.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hemodynamic Characteristics of Elderly Patients with High Blood Pressure
Authors: Hao Chunyan , Duan Hubin , Wang Suping 
Published: June 2021

ObjectiveTo study hemodynamic characteristics of elderly patients with high blood pressure.MethodsThe study selected 94 geriatric patients older than 60 years old in the First Hospital of Shanxi Medical University hospitalized from November 1, 2016 to May 1, 2017. The study included 52 males, 42 females. The basic information were collected including age, sex, weight, and height, and years of hypertension and the level of blood pressure were collected for all hypertensive patients. Non‐invasive hemodynamic monitor records Stroke Volume (SV), Stroke Volume Index (SI), Cardiac Output (CO), Cardiac Output Index (CI), System Vascular Resistance (SVR), Thoracic Fluid Content (TFC) ), Left Ventricular Stroke Work (LSW) and Left Ventricular Stroke Work Index (LSWI), as well as Vascular Elasticity and Contractility Variability.ResultsAccording to blood pressure level classification, there was no significant statistical difference among the general clinical data of all subjects such as age, height, weight, body mass index(P>0.05). According to blood pressure levels of hypertensive patients, the hemodynamic parameters had no obvious variability pattern. And with the age increase, SV, SI, CO, CI, vascular elasticity and cardiac contractility variability reduced, SVR increase; and TFC did not change significantly. In addition, LSW and LSWI in elderly hypertensive patients over 80 years of age changed significantly (P <0.05). According to the level of systolic blood pressure vs diastolic blood pressure, SV, SI, CO, CI, cardiac contractility and other indicators were significantly higher than the control group, and the rest of hemodynamic parameters were not statistically different. As for the high systolic blood pressure group, SV, SI, CO, CI and vascular elasticity are significantly decreased, but SVR, TFC are significantly increased. For both of the high systolic and diastolic blood pressure, LSW and LSWI are significantly increased (P <0.05).ConclusionThe use of non‐invasive hemodynamic tests to obtain different hemodynamic parameters may provide a scientific basis for the diagnosis and personalized treatment of hypertensive patients.Support or Funding InformationThis study was supported by the National Natural Science Foundation Youth Fund (30600637), China Postdoctral Foundation(2014M561207), the Shanxi Province Basic Research Program Youth Science and Technology Research Fund (2010021034‐4, 201601D011119), the Shanxi Scholarship Council of China (2011‐096 and Key Projects No.4), Department of Human Resources and Social Security of Shanxi province, The science and technology research projects of health department of Shanxi Province(2016D011119), The Teaching Reform Program of Shanxi Higher Education, The Education Reform Project of Postgraduate Students in Shanxi Province. The Education Reform Project of Shanxi Medical University.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of the Actin‐binding Protein α‐Adducin for Desmosome Turnover and Keratinocyte Adhesive Function
Authors: Hiermaier Matthias , Wanuske Marie‐Therès , Vielmuth Franziska , Waschke Jens , Spindler Volker 
Published: June 2021

Desmosomes are cell‐cell junctions which provide strong intercellular adhesion and couple the intermediate filament cytoskeleton to sites of cell‐cell contact. We have previously shown that the actin‐binding protein α‐adducin is required for desmosome‐mediated intercellular adhesion. We here tested in more detail the mechanisms underlying α‐adducin‐dependent regulation of desmosomal turnover and adhesion. Experiments were conducted in human keratinocytes with siRNA‐mediated knock‐down of α‐adducin, in knock‐out cell lines obtained with the CRISPR/Cas9 system and in murine knock‐out cells. Dispase‐based dissociation assays confirmed reduced intercellular binding strength in cells lacking α‐adducin. A more immature desmosome state in α‐adducin knock‐outs was indicated by reduced Ca2+‐insensitivity. α‐adducin knockout led to elevated levels of desmoglein (Dsg) 2 and Dsg3 in the membrane. In atomic force microscopy (AFM) single molecule experiments, an increased interaction probability of Dsg3 was detectable in α‐adducin knock‐out cells. This was accompanied by increased amounts of membrane tethers which is in line with a less rigid membrane structure and a role of α‐adducin in organizing the cortical actin cytoskeleton. Ca2+‐depletion/repletion experiments revealed enhanced fragmentation of Dsg3 staining in the membrane in α‐adducin knock‐out cells, indicating dysfunctional desmosome turnover. Indeed, life cell imaging experiments showed less directed intracellular transport of Dsg3‐containing vesicles to the cell membrane whereas fluorescence recovery after photobleaching (FRAP) studies and single molecule imaging demonstrated increased mobility of extradesmosomal Dsg3 in the cell membrane. Interestingly, despite their decreased intercellular cohesion, cells lacking α‐adducin showed slower cell migration in in vitro scratch and ex vivo skin punch biopsy assays. Together, our data indicate that α‐adducin contributes to intercellular adhesion by regulating Dsg3‐dependent adhesive functions, Dsg3 trafficking and desmosome stability.Support or Funding InformationGerman Research Council SP1300/1‐3This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Clinicopathological Assessment of Broiler Chickens Challenged with Field Infectious Bursa Disease Virus after Oral Vaccination Using Phytogenic Mucoadhesive Gum
Authors: Adeniran Gani , Emipke Benjamin Obukowho , Jarikre Theophillus Aghogho , Ola Olawumi , Ohore Godspower , Adigun Oyindamola 
Published: June 2021

The rising socio‐economic loss incurred from mortalities and disharmonized vaccine control programs in poultry production has necessitated the search of adjuvants especially of natural origin. More so, productivity levels of poultry in many African countries fall far below desirable levels because of the economic losses incurred from chick mortality due to infectious bursa disease (IBD). This study determine the level of immune response conferred by Infectious bursa disease vaccine using a mucoadhesive delivery system from a phytogenic origin using the clinic‐pathological response of broilers vaccinated oraly with IBD vaccine using Khaya senegalensis and Cedrela odorata as phytogenic adjuvants and later challenged with the IBD virus. A total of 260 chicks were successfully brooded and raised from day old. The birds were distributed into four groups A to D with an average of 60 birds per group in a complete randomized block design, as A (Gum + IBD Vaccine oral + Virus challenge), B (IBD Vaccine alone oral + Virus challenge), C (Gum alone oral + Virus challenge) and D (No‐Vaccine‐No‐Gum + Virus challenge). Three birds were euthanised per Group for Serum, tracheal and intestinal washings and lymphoid tissue harvest including haderian gland, thymus, lungs, spleen, ileum, cecal tonsils and bursa of Fabricius pre and post vaccinations and post infection during the 7 weeks experiment. Data was analysed using Graph pad prism 21 at α=0.05. All the birds were apparently healthy pre and post vaccinations. The birds exhibited signs of picking and soiling of the vents and feathers with projectile yellowish diarrhoea few birds post infection (B, D). The feathers were ruffled and mortality varied from 0 to 5 in the non‐vaccinated and gum alone vaccinated birds. Pathologically, there was oedematous, hyperplastic to haemorrhagic changes in the bursa, congestive to hyperplastic changes in the spleen with severity in group D and haemorrhages of breast and pectoral muscles in some of the birds that died post infection. No recumbency was recorded in the birds given gum+IBD vaccine and challenged with live virus. Prophylactic application of IBDV vaccines and the Khaya senegalensis gum as phytogenic adjuvants enhanced the chicks immune response and provided protection against IBD.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Molecular and histopathological diagnosis of Fowlpox virus in Chickens in Nigeria
Authors: Adesina Rofiat , Ogunleye Seto , Alaka Olugbenga , Fagbohun Olusegun 
Published: June 2021

Fowlpox is a relatively slow developing disease characterized by discrete, proliferative lesions on the skin of toes, legs or head, and/or mucous membranes of the mouth and upper respiratory tract of birds. Several diseases of birds such as infectious coryza, infectious laryngotracheitis, Mareks, and vitamin A deficiency can be confused with fowlpox, therefore there is need for an accurate and reliable method of diagnosis. Polymerase Chain Reaction (PCR) and histopathology can be used to arrive at the confirmatory diagnosis of the disease. Consequently, fifty samples from suspected cases of fowlpox from backyard poultry in Ibadan, Nigeria were collected, and PCR was used to detect and characterize the open reading frame 168 (39 kDa core protein) gene of the virus. Also, lesions from the eyelids excised were and histopathology was carried out. Thirty‐one out of 50 samples (62%) tested positive for FPV. Histopathology revealed the presence of dermal hyperplasia and Bollinger bodies which are confirmatory of fowlpox. PCR amplification of 39 kDa core protein gene and histopathology provide a reliable diagnosis of fowlpox.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Connective Tissue Dysplasia is a Possible Predictor of Esophageal Variceal Bleeding in Liver Cirrhosis
Authors: Vasylyev Dmytro Volodymyrovych 
Published: June 2021

The aim of this work is to assess the connective tissue skeleton of esophageal varices in patients with liver cirrhosis for the study of morphological predictors of variceal bleeding.Material for morphological research were the fragments of the esophageal wall from the lower third of esophagus taken at autopsy (samples of 10 cases in each group). Four groups of samples were: cirrhotic patients who died due to initial variceal bleeding (group 3), due to recurrent variceal bleeding (group 4). The control (comparing group) consists of fragments of the intact wall of the lower third of the esophagus in patients who died from other pathologies (group 1), and dead from liver cirrhosis, who hadn't pronounced esophageal varices, whose death was not associated with bleeding (group 2).Immunohistochemistry was performed on paraffin sections with a thickness of 5–6 μm using an indirect Coons method. The collagens were identified by monoclonal antibodies (MA) to collagen I, III, IV types (Chemicon International Inc., Daco Cytomation, USA). According to the original technique, it was determined the intensity of the fluorescence of preparation treated with MA and expressed in arbitrary units of fluorescence (AUF).In cirrhotic patients with variceal bleeding revealed the predominance of immature collagen type III (instead of dominated collagen type I) in the composition of the connective tissue of the mucous membrane and submucosal layer of the esophagus, increased intensity of collagen type III in the vascular wall and perivascular space, decrease of fluorescence intensity of collagen type IV in the basal membranes of veins (tables 1, 2). Abnormalities of collagen formation in the basal membranes of the esophageal veins, as well as the replacement of the elastic and muscular elements of the venous walls with immature connective tissue can lead to thinning and rupture of the vein wall.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of P‐glycoprotein Inhibition on Norbuprenorphine‐induced Neonatal Abstinence Syndrome (NAS)
Authors: Salazar Paloma , Higgins William T , Brents Lisa K 
Published: June 2021

Treating pregnant, opioid‐addicted women with the opioid buprenorphine improves mother‐child outcomes, but can cause neonatal abstinence syndrome (NAS), a potentially life‐threatening withdrawal syndrome newborns often develop following chronic prenatal exposure to opioids. NAS severity is independent of maternal buprenorphine dose, suggesting that inter‐individual variance in the pharmacokinetics of buprenorphine may influence NAS. We previously showed that prenatal exposure to the major active metabolite of buprenorphine, norbuprenorphine (NorBUP), can induce NAS. NorBUP is a substrate of the highly polymorphic placental efflux transporter P‐glycoprotein, which transports its substrates from fetal to maternal circulation. We tested the hypothesis that inhibiting P‐glycoprotein increases NorBUP‐induced NAS severity. We administered a subthreshold dose of NorBUP or vehicle to pregnant rats from gestation day (GD) 9 until post‐delivery and treated them twice daily with the p‐glycoprotein inhibitor Elacridar or vehicle on GD18‐21. After delivery, pups were observed for precipitated withdrawal signs following administration of naltrexone or saline. NorBUP and Elacridar together, but not individually, increased naltrexone‐precipitated withdrawal signs, providing the first evidence that P‐glycoprotein activity can substantially modulate the effects of NorBUP on the fetus and may therefore contribute to the uncoupling of maternal buprenorphine dose and NAS severity.Support or Funding InformationThe project described was supported by a Summer Undergraduate Research Fellowship from the American Society for Pharmacology and Experimental Therapeutics, the UAMS Fellow‐to‐Faculty Award (Arkansas Biomedical Institute, Tobacco Settlement Funds), a UAMS Research Scholar Pilot Grant Award in Child Health, and the Translational Research Institute (TRI), grants 1U54TR001629‐01A1 and KL2TR000063 through the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.