bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐aging effect and gene expression profiling of Bumblebee (Bombus terrestris) queen glycosaminoglycan in aged rats
Authors: Ahn Mi Young , Yun Hyung Joo , Hwang Jae Sam 
Published: June 2021

Glycosaminoglycans have been used to diminish deleterious effects associated with aging by preventing destruction of cartilage, bone, discs, and skin. The objective of this study was to evaluate the anti‐aging effect of a newly prepared glycosaminoglycan (GAG) derived from bumblebee (Bombus terrestris) queen (BtQG, 10 mg/kg). Gryllus bimaculatus (Gb, cricket) GAG (GbG, 10 mg/kg) or glucosamine sulfate (25 mg/kg) was used as a positive control. They were intraperitoneally administered to old SD rats as part of their diets for one month. BtQG reduced serum levels of creatinine and BUN. It possessed anti‐lipidemic activities, hepato‐and renal‐protective actions, and maintained normal glucose level in treated rats. BtQG and GbG had marked anti‐inflammatory effects. They inhibited free fatty acid, ALP, and sGPT values. In addition, they showed anticoagulant and antithrombotic effects. The concentration of factor 1 (fibrinogen) was increased in BtQG treated rat plasma. In microarray study, CaG5‐treated rat group shows upregulation of 36 genes compared to the control group, including secretogranin II (Scg2), AP‐1‐regulated protein related ROS DNA damage repair, metallothionein 1a, metallothionein 1M, and alpha‐2 macroglobulin. It also showed 417 downregulated genes, including vimentin, moesin, an d mitochondrial carbonic anhydrase.Support or Funding InformationThis work was supported by the Rural Development Administration Basic Research project, PJ011853This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hybrid biosensing cellulose‐based scaffolds for imaging‐assisted tissue engineering
Authors: O'Donnell Neil , Okkelman Irina A. , Ruane Shannen A. , Timashev Peter , Gromovykh Tatyana I. , Dmitriev Ruslan I. 
Published: June 2021

3D tissue models closely mimic in vivo cell and tissue organization otherwise not seen in conventional cell culture. However, live cell imaging and quantification of cells growing within 3D scaffold are yet to be achieved for success of tissue engineering, cancer biology and regenerative medicine. Here, we aimed to design the environment‐sensitive scaffold material acting both as supporting material and a biosensor for cells growing in it. We chose cellulose‐binding domain of C. fimi CenA protein, termed as CBD (N‐terminal fragment, Ala32‐Thr137) and genetically fused it to either pH (enhanced cyan fluorescent protein, ECFP) or Ca2+ (gCaMP2)‐sensitive proteins. ECFP and gCaMP2 are prospective biosensors for quantitative Fluorescence Lifetime Imaging Microscopy (FLIM). Next, we optimised E. coli expression, purification and folding conditions for these chimeric proteins, achieving yields of ~6 mg/L culture, bright fluorescence (~55% folding rate) and sensitivity to extracellular pH and Ca2+.To assemble the functional biosensing scaffolds using CBD‐fusions, we performed labeling of the three different types of cellulose‐based materials: commercially available nanofibrillar cellulose Growdex™, bacterial cellulose spheres and decellularized plant tissues. Both CBD‐ECFP (pH‐sensitive) and CBD‐gCaMP2 (Ca2+‐sensitive) proteins efficiently labeled scaffolds in concentration‐dependent manner and remained stable under physiological conditions for > 7 days. In a proof‐of‐concept experiments, we tested usability of CBD‐ECFP‐stained Growdex scaffold as an extracellular pH sensor in FLIM: we observed robust and reversible changes in fluorescence lifetime (2.3–2.5 ns) over the range of physiological pH. Further, we tested the biosensing properties of CBD‐ECFP scaffolds, populated with cultured human colon cancer HCT116, mouse embryonic fibroblast (MEF) and primary stem cell‐derived mouse intestinal organoids. All the types of scaffolds were compatible with growth of cells with no evident toxicity, confirmed by experiments with unlabelled scaffolds.In conclusion, we have developed versatile labeling approach for producing biosensing cellulose‐based 3D scaffolds, suitable for different biosensors and types of cell and tissues, including single cells, spheroids and organoids. Such ‘hybrid’ biosensing scaffolds allow for real‐time measurement of extracellular biomolecules using quantitative FLIM microscopy, providing improvements in multi‐parametric imaging of engineered tissue models.Support or Funding InformationScience Foundation Ireland grant SFI 13/SIRG/2144.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exosomal miRNAs derived from specific cardiac progenitor cells exert strong therapeutic effect on myocardial infarction
Authors: Xuan Wanling , Wang Lei , Tang Yaoliang , Ashraf Muhammad 
Published: June 2021

ObjectivemiRNA signatures are unique in exosomes amongst different parent cells. Here, we isolated and characterized exosomes from small molecule induced cardiac progenitor cells (Exo‐CPCiso) and determined their effects on cardiac cells in vitro and on mice hearts following myocardial infarction (MI).Methods and resultsmiR‐373, miR‐367, miR‐520 and miR‐548 were significantly overexpressed in Exo‐CPCiso and these miRNA microarray data were confirmed with real‐time PCR. Go enrichment analysis based on miRNA‐targeted genes showed that biological process included organelle, molecular function, response to stress and mitotic cell cycle. Interestingly, expression of fibrotic genes in cultured fibroblasts stimulated with TGF‐β was significantly downregulated after treatment with Exo‐CPCiso. Loss‐of‐function analysis using miR‐373 inhibitor confirmed that enrichment of miR‐373 was the major contributor to reversion of TGF‐β stimulation in fibroblasts. Moreover, intramyocardial injection of Exo‐CPCiso exerted favorable cardioprotective effects on cardiomyocyte proliferation, angiogenesis and preservation of cardiac function in mice one month post‐MI compared with PBS and Exo‐iPSC treated mice.ConclusionExosomes derived from cardiogenic small molecule induced‐CPCs were highly effective in myocardial repair and functional improvement after MI due to their unique miRNA cargo contents. These data further suggest that cellular source of exosomes has a strong bearing on their therapeutic potential.Support or Funding InformationThis study was supported by the National Institutes of Health grants, RO1 HL126516, HL134354, 2RHL086555 and RO1 AR070029.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
TIMP‐2 Inhibits Triple Negative Breast Cancer Growth and Metastasis through EMT Suppression and Promotion of Vascular Normalization
Authors: Jensen Sandra M. , Kumar Sarvesh , Chowdhury Ananda , Castro Nadia , Shih Joanna , Salomon David S. , Stetler‐Stevenson William G. 
Published: June 2021

Successful tumor cell invasion requires degradation of the extracellular matrix (ECM) by matrix metalloproteases (MMPs), a large family of metalloproteinases that cleave ECM proteins. MMP synthesis and activation is tightly regulated by their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). TIMP‐2 is a multifunctional protein shown to inhibit tumor growth, invasion and metastasis independent of MMP inhibitory activity via mechanisms including alteration of the epithelial to mesenchymal transition (EMT), reduced tumor angiogenesis, and inhibition of VEGF‐A induced vascular permeability. Triple‐negative breast cancers (TNBCs) are highly vascular tumors that exhibit EMT plasticity and extensive metastatic dissemination. We explored the efficacy of recombinant TIMP‐2 (rTIMP‐2) as a preclinical therapeutic using an orthotopic mouse model which phenotypically resembles human TNBC and establishes spontaneous lung metastases. Daily rTIMP‐2 treatment (100 ug/kg/day) was initiated 10 days post tumor cell implantation and continued through day 37. Biweekly tumor measurements [tumor volume) = 1/2(length × width2)] revealed reduced primary tumor growth in rTIMP‐2 treated mice 15 days post inoculation and maximum tumor growth inhibition on day 29. Immunostaining of primary tumors demonstrated increased CK‐18 expression along with decreased CK‐14 and vimentin in rTIMP‐2 treated mice, suggesting reversal of the EMT phenotype by day 32, while lung histology showed a significant reduction in metastatic foci in rTIMP‐2 treated mice at day 52. Moreover, immunofluorescence demonstrates increased pericyte coverage and reduced vascular leakage in rTIMP‐2 treated primary TNBC tumors, showing modulation of vessel morphology and promotion of events consistent with vessel normalization. These findings suggest the therapeutic potential for rTIMP‐2 in the clinical treatment of TNBC.Support or Funding InformationThis work was funded by the NCI Center for Cancer Research Intramural Research Program Project # ZIA SC009179‐25.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dopamine Transporter Allosteric Modulator SRI‐32743 Alters The Effects Of Cocaine On Dopamine Neurotransmission In Adult Mice
Authors: Hager Audrey , Daws Lynette , Ananthan Sam , Beckstead Michael 
Published: June 2021

Cocaine is a highly abused psychostimulant that inhibits dopamine (DA) uptake by blockade of the dopamine transporter (DAT). Despite knowledge and understanding of cocaine's main mechanism of action, there are no FDA‐approved pharmacotherapies for treatment of cocaine‐use disorder. Recently novel allosteric modulators of DAT have been identified that have nanomolar potency to partially inhibit DAT uptake, which may be useful as probes of biogenic amine transporter function and may have therapeutic potential. Here we used both patch clamp electrophysiology in male and female mouse brain slices and high speed chronoamperometry in anesthetized mice to examine the effects of two novel ligands (SRI‐32743 and SRI‐35282) on dopamine neurotransmission and their ability to alter the effects of cocaine. Pretreatment with SRI‐32743 blunted the cellular effects of cocaine by altering DAT function in a concentration‐dependent manner. In addition, SRI‐32743 decreased D2 receptor‐mediated currents of midbrain DA neurons. In contrast, the ligand SRI‐35282 demonstrated less ability to reduce the effects of cocaine. These preliminary results are promising and further exploration of the effects of these allosteric DAT modulators on behavior will be important for determining their potential as pharmacotherapies for the treatment of cocaine‐use disorder.Support or Funding InformationR01DA32701, T32DA031115, F32DA042569, R01MH106978This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reinforcing Potency and Effectiveness of Synthetic Cathinones: Potency versus Selectivity for DAT
Authors: Gannon Brenda M. , Sulima Agnieszka , Rice Kenner C. , Baumann Michael H. , Collins Gregory T. 
Published: June 2021

Synthetic cathinones found in “bath salts” preparations interact with monoamine transporters and function as either cocaine‐like monoamine uptake inhibitors or amphetamine‐like substrates. Abuse of these synthetic cathinones has resulted in regulation of some cathinones internationally. Modifications to the chemical structure of regulated cathinones (e.g., MDPV) produce a series of new cathinones (e.g., α‐PVP, α‐PPP, MDPBP, and MDPPP) which may not be subject to existing regulations. Although MDPV is a more potent and effective reinforcer than cocaine, little is known about the reinforcing effects of other synthetic cathinones. Thus, this study examined intravenous self‐administration of cocaine, MDPV, α‐PVP, α‐PPP, MDPBP, and MDPPP to test the hypotheses that 1) stimulants with greater potency to inhibit the dopamine transporter (DAT) are more potent reinforcers, and 2) stimulants with greater selectivity for DAT relative to the serotonin transporter (SERT) are more effective reinforcers. Potencies to inhibit monoamine uptake at DAT and SERT were determined using synaptosomes prepared from rat brains. Separate groups of male Sprague‐Dawley rats (n=12 per group) were used to generate full dose‐response curves under a progressive ratio (PR) schedule of reinforcement for α‐PVP, α‐PPP, MDPBP, and MDPPP; full dose‐response curves for MDPV and cocaine were also generated in each rat (n=48). Rank order potency to inhibit DAT was MDPV > α‐PVP ≈ MDPBP > MDPPP ≈ α‐PPP ≈ cocaine, while rank order DAT/SERT selectivity was α‐PVP > α‐PPP > MDPV > MDPBP > MDPPP > cocaine. The potency to inhibit DAT correlated with the potency of each drug to maintain responding (MDPV > α‐PVP ≈ MDPBP > MDPPP ≈ α‐PPP ≈ cocaine). Relative reinforcing effectiveness as determined by comparing the maximum number of infusions obtained for each drug under a PR schedule of reinforcement was α‐PVP > α‐PPP ≈ MDPV > MDPBP ≈ MDPPP > cocaine, which correlated with DAT/SERT selectivity. These data suggest that (1) potency at DAT is an important determinant of the potency of each drug to function as a reinforcer, (2) each of these synthetic cathinones functions as a more effective reinforcer than cocaine, and (3) DAT/SERT selectivity is related to reinforcing effectiveness and may predict the abuse‐related effects of novel synthetic cathinones in humans.Support or Funding InformationThese experiments were supported by NIH grants R01DA039146 (GTC) and T32DA031115 (BMG) and the Intramural Research Programs of NIDA (MHB, KCR) and NIAAA (KCR).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Differences in High Fat Diet‐Induced Enhanced Sensitivity to the Locomotor Stimulating Effects of Methamphetamine and SKF 82958
Authors: Ramos Jeremiah , Robles Grace Flores , Gonzalez Adrian , Serafine Katherine 
Published: June 2021

Eating a high fat diet can impact dopamine systems; the same systems that are targeted by drugs of abuse. Rats eating high fat laboratory chow are more sensitive to the behavioral effects of abused drugs, including methamphetamine. Most of the previous research investigating diet‐induced effects on drug sensitivity has used male rats, therefore it is not known if females eating high fat chow are also more sensitive to the behavioral (e.g., locomotor‐stimulating) effects of methamphetamine. Methamphetamine‐induced locomotion is mediated, in part, by dopamine D1 and D2 receptors. While several reports have examined diet‐induced effects on dopamine D2 receptor agonists, it is not known if eating high fat chow also enhances sensitivity of rats to dopamine D1 receptor agonists (e.g., SKF 82958). To test the hypothesis that eating high fat chow enhances sensitivity of male and female rats to drugs that act on dopamine systems, male and female Sprague‐Dawley rats eating either standard laboratory chow (17% kcal from fat) or high fat chow (60% kcal from fat) were tested once per week for 6 total weeks with SKF 82958 (0.01–3.2 mg/kg) or methamphetamine (0.1–3.2 mg/kg) using a cumulative dosing procedure. In an initial cohort of animals (n=3/group), eating high fat chow tended to enhance sensitivity of female rats to SKF 82958 and methamphetamine. This trend was less apparent among male rats eating different diets. Consistent with previous reports, females tended to be more sensitive than males to the behavioral effects of both drugs, regardless of diet. Taken together with previous reports, the present study demonstrates that robust sex differences regarding the behavioral effects of dopaminergic drugs warrant further investigation of both sexes to understand the impact of diet on drug sensitivity. Future research will examine the effects of diet on sensitivity to the reinforcing effects of methamphetamine, to further assess how diet might impact abuse vulnerability.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evaluation of hyperbaric oxygen (HBO2) as a treatment for hyperalgesia associated with naloxone‐precipitated withdrawal in morphine‐dependent mice
Authors: Brewer Abigail Lucille , Shirachi Donald Y. , Quock Raymond M. 
Published: June 2021

Opioid dependence has become a major problem in the United States. Withdrawal from opioid drugs is associated with hyperalgesia (increased sensitivity to a pain stimulus) which may contribute to relapse [Carcoba et al., J Addict Dis 30(3): 258–70, 2012]. Hyperbaric oxygen (HBO2) is 100% oxygen at higher than atmospheric pressure. HBO2 has recently been shown to be effective at decreasing physical signs of withdrawal in morphine‐dependent mice, and there is a growing body of research showing that HBO2 is effective at decreasing pain in clinical conditions and in preclinical modeling [Nicoara et al., Brain Res. 1648:434–7, 2016; Efrati et al., PLOS One 10(5)1–25, 2015; Gibbons at al., Brain Res. 1537:111–6, 2013]. The effectiveness of HBO2 to decrease hyperalgesia caused by opioid withdrawal in an animal model of drug dependence was evaluated in this study. Male and female NIH Swiss mice were made dependent upon morphine by injecting animals s.c. with twice‐daily escalating doses of morphine for 4 consecutive days. On the 5th day, animals were given a final injection of the highest dose of morphine and injected i.p. with 1.0 mg/kg naloxone 8 hours after the final morphine injection. Animals were treated with 30 min of HBO2 at 3.5 atmospheres absolute or room air 60 min prior to naloxone injection. Nociception was evaluated using the tail withdrawal, hot plate and paw pressure tests every 10 min for 30 min after naloxone injection. Baseline levels of nociception for each endpoint were taken prior to induction of morphine dependence. Male and female animals exhibited hyperalgesia in the hot plate and paw pressure tests but not the tail withdrawal test. HBO2 significantly decreased the amount of hyperalgesia in the hot plate and paw pressure tests in male animals. In female animals, HBO2 had no effect on hyperalgesia in the hot plate test but significantly decreased the level of hyperalgesia associated with the paw pressure test. While no hyperalgesia was seen in the tail withdrawal test, HBO2 did produce significant antinociception in male and female animals. These intriguing results show that HBO2 is capable of reducing hyperalgesia associated with opioid withdrawal and warrant further investigation. Furthermore, these results help support previous findings showing that HBO2 may be effective at decreasing symptoms of opioid withdrawal.Support or Funding InformationThis research was supported by the Marchionne 12‐month Fellowship from the Department of Psychology at Washington State University, NIH Grant AT‐007222, and the Honors College Distinguished Professorship from Washington State University.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 the δ‐Opioid Antagonist Naltrindole on the Antinociceptive and Behaviorally Disruptive Effects of Oxycodone in Squirrel Monkeys
Authors: Withey Sarah Louise , Bergman Jack 
Published: June 2021

Opioids remain the most commonly prescribed drug class for the management of moderate to severe pain. Often, high doses that are required for effective analgesia have unwanted effects, ranging from tolerance and dependence, to less severe but still debilitating behavioral disruption. Although most opioid analgesics exert both analgesic and adverse effects primarily through μ‐opioid receptors, recent studies also suggest a role for modulatory interactions between μ‐ and δ‐opioid receptors. For example, δ‐agonists have been proposed to enhance the analgesic potency and efficacy of μ‐agonists, and δ‐antagonists to prevent or diminish the development of tolerance induced by μ‐agonists. Based on these observations, the development of new opioid ligands possessing mixed μ/δ–opioid receptor efficacy has emerged as a novel approach to analgesic drug development. Here, we further study the interaction of these two receptor subtypes by determining whether the δ‐opioid antagonist naltrindole modifies the acute effects of oxycodone on tail withdrawal latency and food‐maintained behavior (reinforcement density, response rate) in squirrel monkeys, using an apparatus for concurrently assaying both behavioral measures.Daily sessions comprised four 5‐min response components, each preceded by a long timeout (10‐min) during which cumulative doses of drugs could be administered. During each component, the completion of ten leverpress responses [fixed‐ratio 10 (FR10)] in the presence of stimulus lights initiated food delivery and a 30‐sec short timeout (STO) during which stimulus lights were off and tail withdrawal latency was measured.Results show that naltrindole (1.0 and 3.2 mg/kg) did not significantly alter oxycodone's dose‐effect function for tail withdrawal latency. However, 3.2 mg/kg naltrindole caused a significant rightward shift in the dose‐effect functions for decreases in food‐maintained behavior. ED50 ratios (i.e., the ratio of ED50 values for the two measures) were calculated as a preclinical estimate of therapeutic utility. Values >1 suggest antinociceptive effects are present at doses that do not cause significant food‐maintained behavioral disruption. The ED50 ratios were 1.26 and 3.92 for oxycodone alone and following 3.2 mg/kg naltrindole, respectively.These results support previous findings that δ‐antagonists may reduce the unwanted adverse effects of μ‐opioid agonists at doses that do not heighten the antinociceptive effects of morphine‐like opioids. Additionally, they provide baseline data for studies of repeated exposure to this type of μ/δ–opioid combination on similar or other behavioral endpoints.Support or Funding InformationSupported by NIDA Grant DA035857This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.