bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMED9 is a poor prognosis marker in hepatocellular carcinoma patients that modulates oncogene trafficking and promote tumorigenesis
Authors: Yang Yi‐Chieh , Lai Tsung‐Ching , Hsiao Michael 
Published: June 2021

PurposeHepatocellular carcinoma (HCC) is the third leading cause of cancer‐related deaths in the world. Due to difficulty of early diagnosis and the treatment in HCC, the prognosis for patients remains poor in the past decade. Therefore, our aim in this study is to establish the screening model to discover novel diagnostic and prognostic markers in HCC patients.DesignSystemic analysis of global gene expressions by using Mass Spectrometry is an attractive approach to identify novel biomarkers for the development of therapeutics and diagnostics. In this study, the fresh protein lysates from paired N/T HCC tissues were analyzed by SDS‐PAGE protein MS/MS and tissue MALDI imaging analysis to identify the putative biomarkers. On the other hand, the frozen sections were applied to MALDI imaging MS system and analyzed by Fleximage and ClinPro software. Selected biomarker signatures were evaluated by the available online databases and immunohistochemistry staining was used to stain N/T paired clinical hepatoma tissue array (n=120) for prognostic value analysis. Immunoprecipitation‐MASS was further used to find the identified marker TMED9 binding proteins.ResultsAccording to the protein ID analysis, 27 proteins were revealed with more than 1.3 fold of T/N ratio. We further validated these genes by TCGA and GEO databases, which recruited the progression data and the paired N/T sample analysis in their cohort. Among these proteins, we found the importance of the TMED9 in HCC progression. The higher TMED9 mRNA and protein levels were significantly observed in the HCC patients. In addition, the patients who had higher TMED9 accompanied with poor prognosis in our Taiwan cohort. Mechanically, the dyregulation of TMED9 in HCC cells altered the trafficking of targeting proteins from ER to Golgi and may also changes their folding, maturation, and post‐translational modifications to modulate their protein functions or stability. The alteration of TMED9 expression changes the metabolism of functional proteins and promotes the tumorigenecity of HCC.ConclusionOur work not only identified the new protein biomarkers in predicting HCC prognosis, but also showed dyregulation of protein trafficking system could promote HCC progression. These new findings may provide new targets for therapeutic intervention in treating patients with HCC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ghrelin Signaling Axis Associates with Poor Prognosis and Promotes Renal Cell Carcinoma Invasion
Authors: Lin Tsung‐Chieh , Hsiao Michael 
Published: June 2021

Increasing studies point out a peptide hormone, ghrelin, playing critical roles in regulating cancer progression. Ghrelin is originally discovered to be expressed at stomach, and functions as an endogenous ligand of growth hormone secretagogue receptor (GHS‐R), which induces growth hormone (GH) release and appetite. Our group previously studied its prognostic significance in cancer patients, and the pro‐metastatic activity in animal model of clear cell subtype of renal cell carcinoma (ccRCC). However, ghrelin's potential function in regulating cell invasion remains obscure. In this study, we performed Ingenuity Pathway Analysis (IPA)‐based analysis of differentially expressed genes in Cancer Cell Line Encyclopedia (CCLE) dataset, which indicates the potential association of Aurora A with ghrelin in ccRCC metastasis. Furthermore, a positive correlation of ghrelin and Aurora A expression level has been confirmed in the dataset including 15 ccRCC cell line and in our ccRCC cell line model. ccRCC patients identified with high ghrelin and Aurora A status are clinically correlated with poor outcome. We further characterized that ghrelin could increase Aurora A level at both protein and RNA level, and the ghrelin‐induced ccRCC in vitro invasion and in vivo metastasis is dependent on Aurora A. To dissect the molecular mechanism, MMP1, 2, 7, 9, 10 and 11 expressions are increased upon ghrelin treatment. Among those matrix metalloproteinases (MMP), MMP10 level is increased and required for the ghrelin‐Aurora axis‐mediated ccRCC invasion. The results discovered in this study indicates a novel signaling mechanism in ccRCC metastasis.Support or Funding InformationMinistry of Science and Technology (107‐2314‐B‐182A‐158 ‐MY3), Taiwan to Dr. Tsung‐Chieh Lin.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lactococcus lactis sp. cremoris elicits protection against metabolic changes induced in females by a Western style diet
Authors: Naudin Crystal , Saeedi Bejan , Owens Joshua , Darby Trevor , Jones Rheinallt 
Published: June 2021

A high sugar and high‐fat diet Western‐style diet can result in significant dyslipidemia, often leading to non‐alcoholic fatty liver disease (NAFLD), with females particularly affected by this diet irrespective of total caloric intake. Dietary supplementation with beneficial bacteria has been advocated as therapeutic intervention to modulate liver adiposity resulting from a Western‐style diet. Here, we assess the activity of beneficial bacteria on modulating the impact of a Western‐style diet in female mice. Of those tested, we show that a previously uncharacterized beneficial bacterium, namely Lactococcus lactis sp. cremoris significantly protected against Western style diet‐induced hepatic steatosis, elevated cholesterol levels, glucose intolerance, increased body mass index (BMI), and adiposity. Due to these effects, we propose the use of L. lactis sp. cremoris as a therapeutic modality to promote metabolic health in individuals suffering adverse health events resulting from a Western style diet.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Contribution of Fractalkine to Incorrect Angiogenesis in Preeclamptic Placentas
Authors: Szukiewicz Dariusz , Szewczyk Grzegorz 
Published: June 2021

Disregarding the multiple research in the field of preeclampsia, the exact pathology remains unclear. The shallow invasion of extravillous trophoblast (EVT) in spiral arteries leads to the development of pregnancy‐induced hypertension, nevertheless the etiological factor is unknown. Disturbed differentiation of EVT and incorrect placental angiogenesis seem to be one of the most important starting points for pathogenetic and etiological concepts in preeclampsia. As fractalkine (chemokine CX3CL1) by the activation of its only receptor CX3CR1 stimulates angiogenesis and integrin‐dependent cell migration, the authors ask the question about the possible role of CX3CL1 in placental angiogenesis in preeclampsia. A total number of 58 pregnant patients were included into the study, preeclampsia was diagnosed in 29 patients, and 29 patients were healthy, normotensive term pregnancies. In all women between 30 and 32 week of pregnancy CX3CL1 level was assessed in plasma using ELISA and the expression of CX3CR1 and angiogenesis score (V/EVTI: vascular/extravascular tissular index) were assessed in placental tissues obtained after delivery. Quantitative immunohistochemistry was applied for assessment of both CX3CR1 expression and V/EVTI in placental sections. For this second purpose, morphometric measurements of the placental microvasculature were performed after immunohistochemistry of endothelial cells with CD‐34 antibody. The average duration of pregnancy in preeclamptic group was shorter by 5,3 weeks than in normotensive pregnancies. CXC3CL1 plasma concentration was significantly lower in preeclamptic patients (mean 279 pg/ml ± 243 vs mean 846 pg/ml ± 418), whereas CX3CR1 expression was significantly (p < 0.05) higher in preeclamptic group. A negative correlation between CX3CL1 level and CX3CR1 expression was observed. Moreover, the V/EVTI value was lowered in preeclampsia (p < 0.05). In conclusion, disturbed placental angiogenesis in preeclampsia may be associated with low plasma fractalkine level.Support or Funding InformationWUM grant: 2M2‐W1‐18This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Detailed Explanation of the Distribution of Atherosclerosis in the Pelvic Cavity
Authors: Khan Sameer Ahmad , Savinova Olga , Beatty Brian Lee 
Published: June 2021

Atherosclerosis is an important indicator for future pathological conditions such as stroke, peripheral artery disease, and coronary ischemic events. Though it is known that atherosclerosis does not present in the systemic circulation evenly, detailed studies of many vascular regions are lacking. In this study, we analyze the atherosclerotic distribution present in the iliac arteries, an area of interest because of the known prevalence of ischemic events in lower extremities and pelvic area ‐ claudication, overactive bladder, and bladder pain syndrome. While hematoxylin and eosin (H&E) stain enables pathophysiological staging of atherosclerotic lesions, it does not illustrate the distribution of calcium deposition in a blood vessel due to low sensitivity and a lack of specificity for calcium. In this study we used alizarin red stain ‐ a histological stain specific for calcium – to increase the detection of calcium deposition in vascular tissues. We used ImageJ analysis to determine percent of alizarin red – positive area (as a measure of calcification) in 6 vessels from 25 cadavers. These vessels were common iliac, external iliac, posterior division on internal iliac, anterior division of internal iliac, superior gluteal, and inferior gluteal arteries. We observed a higher percentage of calcification in the tunica intima rather than the tunica media. We also found a correlation between the percentage of calcification in tunica intima in the common iliac and anterior divisions, as well as the common iliac and inferior gluteal arteries. In tunica media, we found correlation between calcification in the common iliac artery and all other vessels examined except the external iliac. Correlations were also found between medial arterial calcification in external iliac artery and all other vessels (except the common iliac). We found that there are three pairs of vessels, external iliac and posterior division, external iliac and superior gluteal, and external iliac and inferior gluteal arteries with significant medial layer calcification correlations within each subject. Each of these pairs of vessels are significantly far away from each other in the branching pattern. Though speculative, this data could be used in future pathophysiological studies of atherosclerosis both in the pelvic cavity and systemically.Support or Funding InformationNYIT College of Osteopathic Medicine Summer Research ProgramThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Construction of a Common Medication Formulary and Prototype Drug Information for Use in Undergraduate and Graduate Nursing Program Curricula
Authors: Meslin Coralie , Miller Katherine , Veidenheimer Paige , Murphy Patrick J. M. 
Published: June 2021

An essential element in pharmacology course development is the selection of exemplar medications, which are introduced to students as prototype drugs and intended to be representative of the mechanisms, uses, and effects of entire pharmacological categories seen in clinical practice. The purpose of this project was to construct a clinically relevant and pedagogically sound prototype list and most pertinent drug information that could be incorporated across undergraduate and graduate nursing program curricula. Studies have found numerous barriers to effective pharmacologic learning in nursing undergraduate and graduate students, including content saturation and a reliance of memorization‐heavy teaching techniques. While physician‐directed pharmacology education has benefited from consensus pharmacology knowledge objectives and drug lists compiled by the Association of Medical School Pharmacology Chairs, no such counterpart exists for nursing. The concept‐based model of pharmacology education favors using a prototype drug to teach general information for the drug class, and has been proven to effectively respond to proven barriers for pharmacologic learning for nursing students. We developed a formulary to be used by registered nurse (RN), advanced registered nurse practitioner (ARNP), and physician assistant (PA) students utilizing a concept‐based model of pharmacology education. The curated material, which emphasizes medications relevant to family practice and primary care, presents the most applicable nursing interventions, monitoring parameters and side effects for the most commonly used prototype drugs. We collated a list that represents the most commonly used drugs, most frequent and most concerning side effects, as well as pharmacologic information germane to RN, ARNP, and PA licensure examinations. By highlighting these key features of medications, we created a resource that can be used by nursing educators to better serve and educate their students.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Morphine Induces Differential Activation and Cellular Localization of Protein Kinases in the Mouse Periaqueductal Gray
Authors: Ram Akila , Edwards Taylor , Bobeck Erin Nicole 
Published: June 2021

Morphine is a commonly used potent opioid analgesic with very high propensity for tolerance development. The analgesic and tolerance properties of opioids are partially regulated by the midbrain ventrolateral periaqueductal gray (vlPAG). Here, we investigate the intracellular kinase activation and localization patterns in the mouse vlPAG following acute and chronic morphine treatment. Wild‐type mice were treated with morphine (10 mg/kg, i.p.) or saline in a chronic or acute administration paradigm. We performed fluorescence immunohistochemistry to map the localization and activation of extracellular signal‐regulated kinase 1/2 (ERK 1/2), protein kinase‐C (PKC), and protein kinase‐A (PKA). We observed significantly greater activated ERK 1/2 in the vlPAG chronic morphine‐treated animals. We also visualized the co‐localization of ERK 1/2 with the endosomal marker Eea1. We note that phosphorylated PKC tends to localize to the plasma membrane in the vlPAG following chronic morphine treatment and interacts with the μ‐opioid receptor. Further, we observed that although PKA activation is increased following chronic morphine treatment, there is a significant reduction in nuclear translocation of this kinase. Additionally, we examined the cell‐type specificity of kinase activation by co‐localizing these kinases to GAD67 and VGluT neurons that project from the PAG downstream to the Rostral Ventromedial Medulla. Taken together, this study demonstrates a differential activation and localization of ERK 1/2, PKC and PKA, and opens avenues to explore the role of chronic morphine treatment on G‐protein signaling and kinase nuclear transport.Support or Funding InformationThis research is supported by the Department of Biology at Utah State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
In vivo Dependence Liability Assessment of Novel Fentanyl Analogues: Science to Guide drug Policy
Authors: Urquhart Kyle , Fukuda Saki , Gogoi Juoti , Janowsky Aaron , Eshleman Amy , Hiranita Takato , Fantegrossi William E. 
Published: June 2021

The emergence of fentanyl analogues as drugs of abuse raises concern regarding their dependence liability. Following prolonged opioid administration, physical dependence leads to increased use, which facilitates the development of tolerance and the dangers of overdose. In animal models, opioid dependence can be inferred by assessing signs of withdrawal, with vertical jumping being the most sensitive and easily quantified in the mouse. In this study, we aimed to characterize the dependence liability of fentanyl, morphine, and six fentanyl analogues by assessing antinociception and withdrawal signs elicited by each compound in the mouse. First, to determine antinociceptive effects, we used a warm‐water tail withdrawal procedure using both 50°C and 55°C water. Latencies until mice removed their tails from the water were recorded, and fully effective doses were determined using a 10 second cut‐off to prevent tissue damage. Dose effect‐curves were generated to determine the potency (ED50) of each compound for eliciting antinociception. All analogues were less potent than fentanyl but more potent than morphine. Additionally, all test compounds were fully effective in both 50°C and 55°C water. Next, to assess withdrawal, we treated animals with 3 injections of morphine, fentanyl or the various fentanyl analogues spaced 12 hours apart. Following the first two injections on day 1, we precipitated withdrawal on day 2, 3 hours after the final injection of agonist, using the nonselective opioid antagonist naloxone. Withdrawal sessions lasted 20 minutes and the number of vertical jumps were recorded for each session. Antagonist dose‐effect curves for withdrawal jumps were generated first using an agonist dose one‐log unit higher than the fully effective antinociceptive dose and precipitating withdrawal with 3, 10, and 30 mg/kg of naloxone. Next, we used 30 mg/kg of naloxone to precipitate withdrawal using increasing unit doses of each test compoewund since maximal jumping was elicited using 30 mg/kg of naloxone. Agonist dose‐effect curves were generated starting with the lowest fully effective antinociceptive dose and increasing in half‐log units. Our results indicate that all of these fentanyl derivatives are capable of eliciting dependence and offer valuable insight into their abuse potential.Support or Funding InformationThese studies supported in part by DEA/NCTR (224‐16‐0505R),) and the University of Arkansas for Medical ScienVA (D‐15‐OD‐002cesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Differences in Heroin Self‐Administration Behaviors and Heroin‐Induced Receptor Alterations in Rats
Authors: George Brianna , Jones Sara 
Published: June 2021

Despite reports that women are more vulnerable than men to certain features of heroin addiction, including craving and relapse, there are limited numbers of preclinical studies evaluating these phenomena. In addition, the published sex‐comparison studies in preclinical models of heroin addiction have shown conflicting results. For example, Lynch and Carroll (1999) report that female rats acquire heroin self‐administration faster than males, while Stewart et al. 1996 report no differences in acquisition rates between male and female rats. Therefore, this study examined sex differences in several heroin self‐administration behaviors and putative neural correlates. Adult male and female Sprague‐Dawley rats were implanted with jugular catheters and were given access to heroin (FR1 schedule of reinforcement, 0.025 mg/kg/inf; maximum 20 infusions) for 6 hours per day. Acquisition criteria were met when rodents earned all 20 infusions for 2 consecutive days. After acquisition, all animals were placed on a long access (LgA) paradigm, which included unlimited access to heroin (FR1) for 6 hours/day for 10 consecutive days. After completion of LgA, animals were tested for motivation to self‐administer heroin using a progressive ratio (PR) schedule. Finally, we measured basal dopamine dynamics and the ability of kappa opioid receptor (KOR) and D2/D3 autoreceptor agonism to reduce dopamine release in the nucleus accumbens following exposure to heroin self‐administration using ex vivo fast scan cyclic voltammetry (FSCV) in brain slices. Female and male rats acquired heroin self‐administration at similar rates, but females self‐administered more heroin during LgA, had increased loading doses of heroin during the first 10 minutes of LgA sessions, and increased escalation of intake across the 10 LgA sessions compared to males. PR data revealed a rightward shift in the dose‐response curve of the females, indicative of increased motivation to obtain higher doses of heroin. Using FSCV, we found that all rats displayed greater KOR‐ and D3 autoreceptor‐mediated dopamine release inhibition, however, females showed higher levels of activity for both receptors. These results reveal marked sex differences in specific heroin self‐administration behaviors that may be driven by altered receptor functioning within the nucleus accumbens. Future studies elucidating receptor interactions related to sexually dimorphic heroin self‐administration behaviors in rats will be highly informative.Support or Funding InformationT32 DA041349This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Applying label‐free quantitative proteomics to identify profile protein changes in hippocampus of rats after chronic cerebral hypoperfusion
Authors: Wang Yue‐Hua , Yang Ying‐Lin , Cheng Xiao , Lyu Yang , Du Guan‐Hua 
Published: June 2021

Vascular dementia (VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral hypoperfusion. 2‐vessels occlusion (2‐VO) induced by bilateral common carotid artery occlusion has been widely used as a model of VD. In the present study, the global proteins profile of hippocampus in 2‐VO rats was studied using label‐free quantitative proteomics. The results showed that 2‐VO induced learning and memory deficits, motor ability dysfunction, and neuronal plasticity injury in rats. The proteomics results showed that there are involved in up‐regulation of 55 proteins and down‐regulation of 171 proteins in the hippocampus of 2‐VO group vs that of sham group. Gene ontology and signal pathway analysis showed that the regulated proteins are mainly involved in intracellular signaling cascade, metabolic process, oxidation reduction process, oxidative phosphorylation, etc. Furthermore, RT‐PCR results revealed that the mRNA expression of Mt‐nd1, Serpine2, Mrpl15 was significantly decreased and whereas Itapka, Ptpn1, Abracl, Gorasp2 were significantly increased in the hippocampus of 2‐VO rats compared with sham rats. WB result further demonstrated MT‐ND1 expression was consistent with the results of proteomics. The current findings provide new insights into the molecular mechanisms of chronic cerebral ischemia.Support or Funding InformationNational Key Research and Development Program of China (2018YFC0311005), National Natural Science Foundation of China (81473383), National Science and Technology Major Project of China (2018ZX09711001‐003‐019), CAMS Innovation Fund for Medical Sciences (2016‐I2M‐3‐007), and Innovation Fund for Graduate of Beijing Union Medical College (2017‐1007‐02; 2018‐1007‐04).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.