bluuebunny/crossref_metadata_2025_split huggingface dataset:
CP‐25 suppressed the synovial pannus formation in experimental arthritis through Angiotensin □ and its signals
Authors: Yan Shangxue , Cheng Zhuoyu , Wei Wei 
Published: June 2021

ObjectRheumatoid arthritis (RA) is a chronic systemic, autoimmune and inflammatory disease represented as synovitis, pannus formation, adjacent bone erosions, and joint destruction. Paeoniflorin‐6′‐O‐benzene sulfonate (code: CP‐25), a novel ester derivative of paeoniflorin, was evaluated the effects of anti‐angiopoiesis in rats with collagen‐induced arthritis (CIA) and regulated Angiotensin □(Ang□) and its signals pathway on vein endothelial cells.MethodsCIA rats were treated with CP‐25 (50 mg/kg) from days 14 to 35 after immunization. The joint synovial hemodynamics of rats were detected by ultrasonographic methodology and the synovial pannus formation was observed by histopathologic assay. To detect the role of CP‐25 on the synovial pannus formation, human umbilical vein endothelial cells (HUVECs) were co‐stimulated with Ang □ (10−7 mol/L) and TNF‐α (5 ng/ml) in vitro, and CP‐25(10−5 mol/L), Losartan (10−5 mol/L, AT1R blocker) or PD123319 (10−5 mol/L, AT2R blocker) were individual or combined treatment. The effects of CP‐25 on HUVECs functions such as proliferation, migration were detected by Cell Counting Kit‐8 assay (CCK8) or transwell assay. The tube formation were examined by using Matrigel model. The protein expression of AT1R/AT2R signaling pathways in HUVECs were analyzed by western blot.ResultsCP‐25 could alleviate pathological changes and inhibit the synovial pannus formation in CIA rats, decrease regional synovial blood flow signals in the local swelling knee joint. CP‐25 could inhibit HUVEC proliferation, migration as well as tube formation which co‐stimulated with Ang□ and TNF‐α in vitro. CP‐25 showed a synergistic role with Lostan (AT1R antagonist) on down‐regulated the expression of GRK2, p‐ERK1/2, p‐IκBα and p‐P65. Meanwhile, CP‐25 could also inhibit the high level of GRK2, p‐ERK1/2, p‐IκBα and p‐P65 which induced by AT2R antagonist (PD123319).ConclusionCP‐25 could present a potent anti‐angiopoiesis effect in CIA rats and inhibit proliferation, migration as well as tube formation function of the HUVEC through Ang□ and its signals mediating AT1R/AT2R‐GRK2‐ERK1/2‐NF‐κB pathway.Support or Funding InformationThis research was supported by the National Natural Science Foundation of China (No. 81330081; 81673444)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of NLRP3‐Specific Inflammasome Inhibition on Ventricular Arrhythmias in Post‐Infarcted Rats
Authors: Lee Tsung‐Ming , Lin Shinn‐Zong 
Published: June 2021

Myocardial infarction activates the NLRP3 inflammasome that triggers the inflammatory caspase‐1 activation and the IL‐1β maturation. We studied whether a specific inhibitor of the NLRP3 inflammasome, CP‐456,773, can attenuate cardiac sympathetic reinnervation and fatal arrhythmias in a rat model of myocardial infarction. Male Wistar rats were subjected to coronary ligation and then randomized to either saline or CP‐456,773 in in vivo and ex vivo studies. Postinfarction was associated with the activation of NLRP3 inflammasome components and increased the protein and expression of IL‐1β. Immunohistochemical staining of the border zone after infarction revealed macrophages positive for IL‐1β at 3 days post‐MI. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle‐treated infarcted rats compared with sham. Compared with vehicle, infarcted rats treated with CP‐456,773 significantly attenuated myocardial levels of mature caspase‐1 and IL‐1β proteins although there were similar levels of NLRP3 and ASC proteins. CP‐456,773 did not affect NLRP3, ASC, caspase‐1 and IL‐1β expression at mRNA levels. Sympathetic hyperinnervation was blunted after administering CP‐456,773, as assessed by immunofluorescent analysis and western blotting and real‐time quantitative RT–PCR of nerve growth factor. Arrhythmic scores in the CP‐456,773‐treated infarcted rats were significantly lower than those in vehicle. Ex vivo studies showed no additional effect of anti‐IL‐1β antibody on attenuated levels of NGF compared with CP‐456,773 alone. CP‐456,773 protects ventricular arrhythmias by attenuating sympathetic innervation via NLRP3 inflammasome/IL‐1β‐dependent pathways, which converge through the attenuated formation of nerve growth factor in infarcted rats.Support or Funding InformationnilThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neuropilin‐1 Deficient Macrophages as a Treatment Strategy for Glioblastoma
Authors: Caponegro Michael D. , Tsirka Stella E. 
Published: June 2021

Post‐diagnosis survival of grade IV glioblastoma (GB) is a dismal 14 months in patients receiving standard of care therapy. With the development of immunotherapeutic strategies targeting non‐cancerous, stromal cells of the tumor microenvironment (TME), new avenues are being pursued in clinical trials and pre‐clinical animal models of advanced GB. Glioma‐associated microglia/macrophages (GAMs) of the TME promote chemoattraction, immune suppression, neoangiogenesis, and tumor cell survival, which parallels tumor‐infiltrating macrophage behavior of other solid malignancies. GAMs are now recognized as a potentially practical immunotherapeutic target in GB. Previously in our lab, we have shown that GAM‐specific deletion of the cell surface co‐receptor Neuropilin‐1 (NRP1) drastically reduces pro‐tumorigenic behavior of infiltrating microglia and/or macrophages in murine glioma by reducing immunosuppressive tendencies and neoangiogenesis. As an extension to our genetically‐ablated mouse model, we present here a platform by which these NRP1‐deficient monocytic cells can be harvested ex vivo and locally delivered into the TME of the bulk glioma lesion, to exert anti‐tumorigenic effects. To our knowledge, this is the first attempt to deliver cells of monocytic origin intratumorally as a therapeutic option.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nicotinic Acetylcholine Receptors of α7 and α4β2 Types Mediate the Nicotine Counteraction of Impaired Baroreceptor Function in Endotoxic Rats
Authors: Sallam Marwa Y , El‐Mas Mahmoud M , El‐Gowilly Sahar M 
Published: June 2021

Autonomic dysfunction and reduced arterial baroreceptor activity are prominent features of sepsis. Given the defensive role of the cholinergic antiinflammatory pathway against endotoxic manifestations, agonist and antagonist studies were employed in the current study to identify the roles of α7 and α4β2 nAChRs in impaired reflex chronotropic function caused by endotoxemia in conscious male rats. Endotoxemia was induced by i.v. administration of lipopolysaccharides (LPS, 10 mg/kg) and baroreflex activity was measured by the vasoactive method. The latter involves the assessment of reflex chronotropic responses evoked by increases (phenylephrine, PE) or decreases (sodium nitroprusside, SNP) in blood pressure. Slopes of baroreflex curves were taken as a measure of baroreflex sensitivity (BRS). The data showed that the shifts caused by LPS in baroreflex curves generated by PE or SNP as well as the associated decreases in slopes of the curves (BRSPE, from −2.0±0.2 to −1.2±0.1 beats/min/mmHg; BRSSNP, from −3.7±0.3 to −2.1±0.2 beats/min/mmHg) were dose‐dependently reversed by subsequent i.v. administration of nicotine (25, 50, or 100 μg/kg). Such nicotine effects disappeared after selective blockade of α7‐nAChRs or α4β2‐nAChRs by intracisternal administration of methyllycaconitine (MLA) and dihydro‐β‐erythroidine (DHβE), respectively. We also report that the corrective effects of nicotine on BRSPE were replicated in rats treated with i.v. PHA‐543613 (α7‐nAChR agonist; 0.2–2.0 mg/kg) or 5‐iodo‐A‐85380 (5IA, α4β2‐nAChRs agonist; 0.01–0.1 mg/kg) in dose‐related fashions. Conversely, while the depressed BRSSNP of endotoxic rats was preserved after individual treatment with PHA or 5IA, improved BRSSNP was only seen after the combined exposure to the two drugs. Collectively, functional α7 or α4β2 nAChRs is essential for the demonstration of the alleviation by nicotine of baroreflex dysfunction induced by endotoxemia. Moreover, the precise roles of the homomeric α7 and heteromeric α4β2 nAChRs depend on the nature of the reflex chronotropic response (bradycardia vs. tachycardia).Support or Funding InformationSupported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Involvement of KCa2.3 Channels in Relaxation of Erectile Tissue is Altered in Type 2 Diabetic Mice
Authors: Steffensen Simon Gabriel Comerma , Fais Rafael Sobrano , Beck Lilliana , Mogensen Susie , Simonsen Ulf 
Published: June 2021

IntroductionActivation of endothelial small conductance calcium‐activated K+ channels (KCa2.3 or SK3) and intermediate conductance calcium‐activated K+ channels (IK or KCa3.1) leads to vascular relaxation. Our previous studies have shown that KCa2.3 down‐regulation diminishes erectile function; this channel it is the most expressed KCa channel in the endothelium of corpus cavernosum. In the present study we hypothesized that KCa2.3 channel function is altered in erectile tissue of type 2 diabetic animals.Materials and MethodsErectile function was measured in diabetic db/db mice and was compared to heterozygous control animals. Corpus cavernosum strips were mounted for isometric tension recording, and they were processed for qPCR or Western Blot. The current research was performed in accordance to FASEB Statement of Principles for the use of Animal in Research and Education.ResultsIn anesthetized diabetic db/db mice erectile function was diminished compared to control animals. Concentration‐dependent contractions to noradrenaline were increased in corpus cavernosum strips from db/db compared to strips from control mice. Apamin, a blocker of KCa2 channels inhibited acetylcholine relaxation in corpus cavernosum from db/db and control animals, being less effective in db/db compared to control animals. NS309 (0.5 μM), an activator of KCa2 and KCa3.1 channels, potentiated concentration‐response curves for acetylcholine in corpus cavernosum from control, but this was not the case in corpus cavernosum from db/db mice. SNP relaxation was similar in corpus cavernosum from db/db and control animals. KCa2.3 gene and protein expression was increased in corpus cavernosum from db/db mice, nevertheless protein expressed in aorta was unchanged.ConclusionsOur results suggest that in type 2 diabetes KCa2.3 channel expression is unchanged in the systemic circulation, and upregulated in erectile tissue. In erectile tissue noradrenaline contraction is increased and the effect of NS309 reduced which may be related to impaired KCa2.3 channel function. These changes may contribute to impairment of erectile function in diabetes.Support or Funding InformationAarhus University, Novo Nordisk Foundation and the Danish Research Council.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glucagon receptor antagonists for diabetes mellitus treatment: A systematic literature review
Authors: Miyama Kelle , Elbarbry Fawzy , Bzowyckyj Andrew 
Published: June 2021

ObjectiveThe objective of the study was to evaluate the available literature on the safety and efficacy of glucagon receptor antagonists for the treatment of diabetes mellitus.MethodsA search of PubMed using the terms “glucagon receptor antagonist AND diabetes” and “Pharmacokinetics AND pharmacodynamics AND glucagon receptor antagonist” was conducted. Initial study selection identified 398 articles. Titles and abstracts were reviewed for relevance, resulting in a total of 377 articles excluded (e.g. use of GLP‐1 or GIP agonist, combination therapy). The full texts of the remaining articles were evaluated and their references reviewed to identify additional articles meeting inclusion/exclusion criteria (n=2); resulting in 23 total studies included.ResultsOf the current literature evaluated, 13 studies were conducted in animal models, whereas 11 studies were conducted in humans, with one study occurring in both. A few compounds were identified as having promise for diabetes management including: LY2409021, LGD‐6972, REGN1193, Bay 27‐9955, PF‐06291874, MK‐3577. Findings from the animal and human studies were similar. Both study types demonstrated consistent glucose lowering effects with low rates of hypoglycemia, but varied by agent in regards to alterations in other surrogate measures (e.g. blood pressure, HDL‐C, LDL‐C, Triglycerides, AST, ALT), pharmacokinetics, and adverse effect patterns. Most adverse effects identified were minor and reversible. Efficacy of glucose lowering effects in animal models showed a reduction in blood glucose ranging in magnitude of 57–98 mg/dL. Human models demonstrated a lowering in FPG ranging in magnitude of 27–57 mg/dL.ConclusionGlucagon receptor antagonists have shown promise in animal and human models as an alternative option for diabetes mellitus treatment. The glucose lowering benefit with low rates of hypoglycemia is promising. Ongoing research is needed to further assess their efficacy and safety over the long‐term.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of gut microbiome modulation on alpha/beta diversity, persistent pain‐depressed behaviors and inflammation in female Fisher rats with or without voluntary access to running wheels
Authors: Payne Emily , Brackin Rebecca , Harrington Kylee , Richard Philomena , Couture Sarah , Rieder Courtney , Sannajust Sebastien , King Tamara , Mattei Lisa , Lee Jung‐Jin , Bittinger Kyle , May Meghan , Stevenson Glenn W. 
Published: June 2021

Given the reported effects of gut microbiome modulation on local gut inflammation and intestinal pain, it is possible that gut microbiota regulate persistent or chronic pain conditions that are distal to the gut, including pain states in the extremities. This study evaluated the effects of gut microbiome modulation on formalin pain‐depressed behaviors and formalin‐induced paw inflammation in female Fisher rats. Pilot data indicate that (1) a two‐week regimen of the narrow‐spectrum gram‐positive antibiotic vancomycin (500mg/L) in drinking water depleted Firmicutes and Bacteroidetes diversity / density in rats with or without access to running wheels; (2) formalin alone (0.5, 2.5, 5%) produced concentration‐dependent biphasic licking behavior of injured hind paw across 60 min and concentration‐dependent depression of voluntary wheel running for 7 consecutive days; (3) two‐week antibiotic treatment prior to formalin administration had a protective effect manifested as attenuation of Phase II formalin scores, and complete reversal of formalin pain‐depressed wheel running for 7 consecutive days; (4) the protective effects of vancomycin on formalin pain‐related outcomes were associated with divergent changes to proteobacteria in sedentary vs. voluntary exercised rats. These data indicate that a narrow spectrum gram‐positive antibiotic can have lasting protective effects on persistent pain‐related behaviors and that associated changes to gut microbiota vary as a function of sedentary vs. exercise condition. Parallel mechanistic studies are currently assessing the efficacy of probiotic and fecal microbiota transplant procedures vs. opioid compounds to block antibiotic‐induced modulation to formalin pain‐related outcomes.Support or Funding InformationThis research supported by a NIH COBRE grant (P20GM103643) that supports an animal behavior core facility, and a COBRE Pilot award and NIAMS R15 AREA grant (AR054975) to G.W.S.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Polysaccharides from Dendrobium Officinale on Intestinal Barrier Functions of Rats Induced by Excessive Consumption of High Fat and Sucrose Diet
Authors: Yan Meiqiu , Si Qiuqiu , Su Jie , Yu Jinjin , Lei Shanshan , Li Bo , Wang Ting , Yang Zhiyuan , Chen Suhong , Lv Guiyuan 
Published: June 2021

Accumulating evidence indicates that improper diet can damage host gut barrier function and increase endotoxin level in the bloodstream. Dendrobium officinale as a traditional herb medicine mainly used for diabetes showed obvious protective effect in various metabolic diseases. Meanwhile it has obvious enterogastric function, such as modulating of enteric dysbacteriosis, improving gut barrier, promoting digestion, etc. Polysaccharides have been verified are the main effective fraction. In present study, polysaccharides from Dendrobium Officinale(DOP) was given via oral administration to rats for 10 weeks to investigate its effects on intestinal barrier functions, including the mechanical barrier and biological barrier function. It was found that DOP administration could significantly down‐regulate the level of TC, GLU and HOMA‐IR, up‐regulate the expression of claudin‐1, occludin in ileum, markedly improve the levels of interleukin‐6 (IL‐6) and tumor necrosis factor ‐α(TNF‐α), and decrease the level of diamine oxidase (DAO) and lipopolysaccharides (LPS) in serum. Meanwhile, the polysaccharide decreased the Firmicutes‐to‐Bacteroidetes ratio and upregulated the production of acetate, propionate and butyrate. Our results indicated that the polysaccharides from stem of Dendrobium Officinale might ameliorate insulin resistance induced by high fat and sucrose diet by regulate the intestinal barrier functions.Support or Funding InformationThe project supported by the National Natural Science Foundation of China (81703772,81673638), National Key R&D Program of China (2017YFC170202, 2017YFC170203), Natural Science Foundation of Zhejiang Province (LQ17H280005), Opening Project of Zhejiang Provincial First‐rate Subject (Chinese Traditional Medicine), Zhejiang Chinese Medical University (Ya2017010)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation
Authors: Kiss Tamas , Fulop Gabor A , Tarantini Stefano , Balasubramanian Priya , Yabluchanskiy Andriy , Farkas Eszter , Bari Ferenc , Ungvari Zoltan , Csiszar Anna 
Published: June 2021

Aging‐induced pro‐inflammatory phenotypic alterations of the cerebral vasculature critically contribute to the pathogenesis of vascular cognitive impairment. Cellular senescence is a fundamental aging process that promote inflammation, however, its role in cerebrovascular aging remains unexplored. The present study was undertaken to test the hypothesis that advanced aging promotes cellular senescence in the cerebral vasculature. We found that in cerebral arteries of 24 month old mice expression of molecular markers of senescence (p16INK4a, p21) is up‐regulated as compared to that in young controls. Induction of senescence programs in cerebral arteries is associated by an up‐regulation of a wide range of inflammatory cytokines and chemokines, which are known to contribute to the senescence‐associated secretory phenotype (SASP) in vascular cells. Age‐related cerebrovascular senescence and inflammation are associated with neuroinflammation, as shown by the molecular footprint of microglia activation in the hippocampus. Genetic depletion of the pro‐survival/anti‐aging transcriptional regulator Nrf2 exacerbated age‐related induction of senescence markers and inflammatory SASP factors and resulted in a heightened inflammatory status of the hippocampus. In conclusion, our studies provide evidence that aging and Nrf2 dysfunction promote cellular senescence in cerebral vessels, which may potentially cause or exacerbate age‐related pathology.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Is hsa‐miR‐21‐5p a potential biomarker of vulnerable atherosclerotic plaque?
Authors: Kowara Michał Krzysztof , Paskal Wiktor , Gondek Agata , Opolski Grzegorz , Cudnoch‐Jêdrzejewska Agnieszka Barbara 
Published: June 2021

INTRODUCTIONVulnerable atherosclerotic plaque localized in coronary arterial bed is clinically important, because its rupture leads to a thrombus generation, which can totally occlude the culprit coronary artery causing myocardial infarction. Therefore finding a biomarker characteristic for a vulnerable plaque is warranted. A potential candidate is hsa‐miR‐21‐5p, a microRNA particle which promotes atherosclerotic plaque destabilization by increasing MMP‐9 expression and by enhancing local inflammatory state (negative regulation of SMAD‐7 expression).AIM OF THE STUDYAssessment, whether hsa‐miR‐21‐5p serum level differs significantly in patients with unstable coronary artery disease comparing to patients with stable coronary disease and myocardial infarction.MATERIALS AND METHODSPatients (n=42) were divided into 5 groups – ST‐segment elevation myocardial infarction (STEMI) (n=8); non‐ST segment elevation myocardial infarction (NSTEMI) (n=10), unstable angina (n=8), stable coronary artery disease (sCAD) (n=8) and 8 healthy volunteers (W). Serum samples were taken and hsa‐miR‐21‐5p relative expression level (in reference to hsa‐miR‐191‐5p and hsa‐miR‐93‐3p) was measured in each sample by RT‐qPCR. Serum samples form STEMI, NSTEMI and UA groups were taken within 24 hours of admission, before coronary angiography procedure. The results were statistically assessed on STATISTICA 13 programme.RESULTSThe results have shown, that hsa‐miR‐21‐5p serum level differs significantly between STEMI and UA group (5,955 vs 2,311; p= 0,04). No significant differences occurred between UA and CAD groups (2,311 vs 1,990; p=0,66) and between CAD and healthy volunteers (1,99 vs 1,79; p = 0,77). Comparison between other groups (STEMI vs NSTEMI, NSTEMI vs UA) showed no statistically significant differences in hsa‐miR‐21‐5p relative expression level.CONCLUSIONSThe study has shown no evidence supporting the hypothesis, that hsa‐miR‐21‐5p is a biomarker of a vulnerable atherosclerotic plaque, because its expression level didn't vary significantly between UA and CAD group. However, a significant difference in hsa‐miR‐21‐5p serum level between STEMI and UA group was found. This correlation could indicate, that hsa‐miR‐21‐5p plays a role on initial stages of myocardial ischemia and infarction.Support or Funding InformationNone
The relative expression level of hsa‐miR‐21‐5p between different study groups (STEMI vs UA; UA vs CAD; CAD vs W).imageThe relative expression level of hsa‐miR‐21‐5p between different study groups (STEMI vs UA; UA vs CAD; CAD vs W).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.