bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Compromised Renal Vasodilations of Adenosinergic Origin in Endotoxic Rats is Reversed by Nicotine: Role of the nAChRs/Heme Oxygenase‐1 Pathway
Authors: Wedn Abdalla M , El‐Gowilly Sahar M , El‐Mas Mahmoud M 
Published: June 2021

The nicotinic/cholinergic antiinflammatory pathway protects against acute kidney injury and other end organ damages induced by endotoxemia. In this study we tested the hypothesis that functional α7‐nAChRs/heme oxygnase (HO) pathway is imperative for the nicotine counteraction of renovascular dysfunction caused by endotoxemia in rats. Renal vasodilations were induced by cumulative bolus injections of acetylcholine (ACh, 0.01–7.29 nmol) or ethylcarboxamidoadenosine (NECA, adenosine receptor agonist, 1.6–100 nmol) in isolated phenylephrine‐preconstricted perfused kidneys. The data showed that 6‐hr treatment with i.p. lipopolysaccharide (LPS, 5 mg/kg) elevated biochemical indices of renal function (serum urea and creatinine) and reduced renal vasodilations caused by NECA. The specificity of the LPS interaction with NECA responses was indicated by the lack of similar attenuation in renal vasodilations induced by ACh. Additionally, the LPS effects were not sex‐related because they were observed in both male and female preparations. The attenuated vasodilatory action of NECA and elevated biomarkers of kidney function in endotoxic rats were reversed upon concurrent treatment with bilirubin (5 mg/kg), but not hemin (HO‐1 inducer, 10 mg/kg) or tricarbonyldichlororuthenium (II) dimer (carbon monoxide‐releasing molecule, 10 mg/kg). Likewise, the LPS effects were dose‐dependently abrogated by nicotine co‐treatment (0.5, 1 and 2 mg/kg). The blockade of α7‐nAChRs (methyllycaconitine citrate, 2 mg/kg) or inhibition of HO‐1 (zinc protoporphyrin, 10 mg/kg) blunted the advantageous effects of nicotine on renal endotoxic manifestations. The Kaplan‐Meier survival curve analysis showed that the increase in mortality rate caused by LPS disappeared in the presence of nicotine or bilirubin. Together, the current biochemical and pharmacological evidence suggests key roles for α7‐nAChRs and the bilirubin byproduct of the HO‐1 signaling in the nicotine counteraction of renal dysfunction and reduced adenosinergic vasodilator capacity.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.
Repeated non‐invasive limb ischemic preconditioning attenuates myocardial ischemia‐reperfusion injury in diabetic rats by up‐regulating hexokinase II
Authors: Zhang Dengwen , Wang Sheng , Ye Xiaodong , Cai Yin , He Yi , Xia Zhengyuan 
Published: June 2021

BackgroundIschemic heart disease is the leading cause of mortality in patients with diabetes mellitus. Although remote ischemic preconditioning achieved by non‐invasively occluding the brachial artery (non‐invasive limb ischemic preconditioning, NLIP) lost its cardioprotection in diabetes, our recent study demonstrated that repeated NLIP (rNLIP, applying 3 cycles of 5 minutes occlusion/5 minutes reperfusion in a unilateral hindlimb daily for 3 days) reduced myocardial infarction, but the mechanism is unclear. Hexokinase II (HKII) is a key glycolytic enzyme that regulates cell survival when bonds to out mitochondrial membrane. However, it is unknown whether HKII is involved in the cardioprotection of diabetic myocardial ischemia/reperfusion(I/R) injury conferred by rNLIP and warrants investigation.Methods and ResultsType 1 diabetic rat model was established by intravenous injection of streptozotocin (60 mg/kg). Myocardial I/R was induced by ligating the left anterior descending artery for 30 minutes followed by 2 hours reperfusion. The results showed that HKII was down‐regulated in the myocardium of diabetic rats(p<0.05, vs. non‐diabetic rats), while myocardial I/R injury was aggravated, as evidenced by increases in post‐ischemic myocardial infarct size, lactate dehydrogenase and circulating levels of troponin I (cardiac injury markers, p<0.05 vs. non‐diabetic rats with I/R), concomitantly with enhanced cardiac apoptosis level (reduced Bcl2/Bax ratio, increased cleaved caspase‐3 level and more TUNEL‐staining positive cells) and aggravated inflammatory responses (increased mRNA levels of pro‐inflammatory cytokines IL1β, IL6 and TNFα). rNLIP significantly up‐regulated the expression of HKII in the myocardium of non‐diabetic and diabetic rats (the up‐regulation level is more pronounced in diabetic rats). The rNLIP‐induced HKII expression in diabetic rats was paralleled by reductions in myocardial infarct size, cardiac apoptosis and inflammatory responses.ConclusionrNLIP attenuates diabetic heart I/R injury through inhibiting cell apoptosis and inflammatory response via up‐regulation of HKII in cardiomyocytes and that targeting HKII expression may be a potential clinical therapeutic intervention for the management of ischemic heart disease in diabetes.Support or Funding InformationThe study was supported by Guangdong Natural Science Foundation (2018A030313535, Guangdong, China) and HMRF (05161826) of Hong Kong.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Aging Healthy, or with Diabetes, is Associated with ACE2/ACE Imbalance in the Hematopoietic Stem Progenitor Cells
Authors: Joshi Shrinidh , Gomez Samuel , Duran‐Mendez Miguel , Quiroz‐Olvera Julio , Garcia Charles , Jarajapu Yagna PR 
Published: June 2021

Bone marrow‐derived hematopoietic stem progenitor cells (HSPCs) have vasoreparative functions and are physiologically mobilized into circulation. Aging or diabetes increases risk for cardiovascular diseases and are known to be associated with impaired HSPC functions. Angiotensin converting enzyme (ACE) and ACE2 are primary enzymes of cardiovascular detrimental and protective axes of renin‐angiotensin system (RAS). Angiotensin‐(1‐7) is generated largely by degradation of Ang II by ACE2 and produces vasoprotective functions by activating Mas receptor. We have shown that Ang‐(1‐7) reverses diabetic dysfunction in murine and human HSPCs. This study tested the hypothesis that aging healthy or with diabetes is associated with imbalance in the vascular protective and detrimental axes of RAS in HSPCs. Peripheral blood samples were obtained from either male or female healthy (n=23) or diabetic (n=21), both type 1 and type 2, individuals of age ranging from 25 to 87 years. Lineage‐negative (Lin−) or CD34+ HSPCs were enriched from mononuclear cells. ACE and ACE2 activities in the cell lysates were determined by using enzyme‐specific fluorogenic substrates. Enzyme activities are expressed as arbitrary fluorescence units that is inhibitable by the enzyme‐selective inhibitors of ACE or ACE2, captopril and MLN‐4760, respectively. ACE2/ACE activity ratios in HSPCs in different individuals are plotted against the respective ages. ACE2/ACE is negatively correlated with the age in healthy (Pearson's r=−0.88, P<0.0001) and in diabetic individuals (Pearson's r=−0.82, P<0.0001). As predicted, a negative correlation was observed with ACE2/ACE vs HbA1C (Pearson's r=−0.899, P<0.0001). These results imply that vascular protective axis of RAS is dysfunctional in HSPCs of aging individuals either healthy or diabetic, which is likely to be an underlying mechanism of the impaired reparative functions in HSPCs. Molecular or pharmacological approaches that enhance ACE2 activity or expression could be of great promise in reversing the age‐ or diabetes‐associated dysfunctions and restore cardiovascular health.Support or Funding InformationNational Institute of General Medical Sciences (NIGMS), and National Institute of Aging (AG056881)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ovine Mucosal Enoxaparin Exhibit Comparable Pharmacokinetic Profiles to Porcine Mucosal Enoxaparin
Authors: Rangnekar Varun , Kouta Ahmed , Jeske Walter , Yao Yiming , Hoppensteadt Debra , Niverthi Manoj , Duff Rick , Fareed Jawed 
Published: June 2021

BackgroundLow Molecular Weight Heparins (LMWH) such as Enoxaparin are currently derived from porcine mucosal heparin (PMH), the same depolymerization methods can be used to obtain enoxaparin from unfractionated heparin from other sources. The purpose of this study is to compare the pharmacokinetics of ovine mucosal enoxaparin (OME) with that of porcine mucosal enoxaparin (PME).Materials and MethodsBranded Enoxaparin (Lovenox, Sanofi‐Aventis, Bridgewater, NJ) and three batches of OME (Suzhou Ronnsi Pharma, Suzhou, China) were used. Following anesthesia, a baseline blood sample was collected from primates (Macaca mulatta; n=4). LMWH was administered subcutaneously (SC) at a dose of 1 mg/kg. Additional blood samples were collected at various times (2,4,6 hours). Anti‐Xa and anti‐thrombin assays were used to calculate pharmacokinetic parameters. Tissue factor pathway inhibitor antigen levels were also measured using an ELISA method.ResultsIn the samples collected at 2, 4, and 6 hours, comparable levels of branded PME and the three batches of OME were observed using both anti‐Xa and anti‐thrombin assays. The pharmacokinetic parameters such as biologic half‐life, Cmax, volume of distribution, and clearance were comparable for both the ovine and porcine enoxaparin. Tissue Factor Pathway Inhibitor levels returned to baseline levels by 6 hours in OME, but remained slightly elevated with PME.DiscussionAt a 1 mg/kg SC dosage, three OME preparations produced comparable anti‐Xa and anti‐IIa effects which were similar to the ones observed with PME. The PK parameters calculated based on this data were also comparable for both groups. It is concluded that the SC pharmacokinetics of the three batches of OME were not only comparable between batches, but were also similar to the branded product.Support or Funding InformationNone.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Amelioration of Diabetic Nephropathy Using a Retinoic Acid Receptor β2 Agonist
Authors: Trasino Steven , Tang Xiao‐Han , Shevchuk Maria M. , Choi Mary , Gudas Lorraine J 
Published: June 2021

Vitamin A (VA) and its derivatives, known as retinoids, play critical roles in renal development through retinoic acid receptor β2 (RARβ2). Disruptions in VA signaling pathways are associated with the onset of diabetic nephropathy (DN). Despite the known role of RARβ2 in renal development, the effects of selective agonists for RARβ2 in a high fat diet (HFD) model of DN are unknown. Here we examined whether AC261066 (AC261), a highly selective agonist for RARβ2, exhibited therapeutic effects in a HFD model of DN in C57BL/6 mice. Twelve weeks of AC261 administration to HFD mice was well tolerated, with no observable side effects. Compared to HFD mice, HFD + AC261 treated mice had improved glycemic control and reductions in proteinuria and urine albumin to creatinine ratio. A number of molecular hallmarks of DN were mitigated in HFD + AC261 treated mice, including reductions in tubule lipid droplets (LDs), podocyte (POD) effacement, endothelial cell (EC) collapse, mesangial expansion, and glomerular basement membrane (GBM) thickening., Mesangial and tubule interstitial expression of the myofibroblast markers α‐smooth muscle actin (α‐SMA) and type IV collagen (Col‐IV) was lower in HFD + AC261 treated mice compared to HFD alone. Ultrastructural and immunohistochemistry analyses showed that, compared to HFD mice, HFD + AC261 treated mice showed preservation of POD foot process and slit diaphragm morphology, and an increase in the levels of slit‐diagram protein podocin and the transcription factor WT1 in PODs. Given the need for novel DN therapies, our results warrant further studies of the therapeutic properties of AC261 in DN.Support or Funding InformationThis research was supported in part by Weill Cornell funds and by NIH R01DK113088 to LJG. SET was supported by the National Institutes of Health (T32 CA062948)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evaluation of Cytotoxic Effect of L‐Histidine Methyl Ester Hydrochloride of Amphotericin‐B (A21) on Tumoral Cells
Authors: Escobar‐Resendiz Rubi , Reyes‐Esparza Jorge , Ortega Ivan , Rodriguez‐Fragoso Lourdes 
Published: June 2021

The term cancer encompasses a hundred diseases that are caused by damage and mutations in the genome. Damage to DNA can be caused by the increase of free radicals, which when interacting with nitrogenous bases and deoxyribose generate highly mutagenic products. The alterations in the genome trigger the activation and / or suppression of proteins that cause the cell to lose the regularization of the cell cycle and its capacity to induce apoptosis, which leads to an uncontrolled proliferation. Lung cancer is one of the leading causes of death worldwide, its main treatment is chemotherapy. Previous studies have shown that amphotericin B (AmB) has antineoplastic effects and potentiates the effect of other antineoplastics. L‐Histidyl methyl ester hydrochloride of amphotericin B (A21) is a derivative of AmB developed by researchers of the UAEM and UNAM. Preclinical studies have shown that the derivative has the same antifungal pharmacological efficacy, but less toxicity than AmB. Given that the AmB derivative is equally effective, but less toxic than the AmB, it is essential to know whether said derivative has the same antineoplastic capacity as its predecessor, and thus may be considered as an equally effective alternative treatment, but with a lower degree of toxic effects for the organism. Therefor, the aim of this work was to evaluate whether the derivative A21 produces cytotoxic effects in tumor cells.A549 cells (ATCC CCL‐185) were used: Non‐small cell lung carcinoma cells (Human). They are grown in supplemented F‐12 Ham Kainghn's Modification medium. The cells received the following treatments: cisplatin and AmB at 3, 7, 15 and 20 μg/mL and Derivative of AmB at 3, 7, 15, 30, 60 and 120 μg/mL. The evaluation of cytotoxicity was performed by an MTT assay. Cell morphology was assessed by Giemsa staining. Subsequently, a cell proliferation assay using MTT will be performed, oxidative stress will be evaluated (ROS‐GloTM H2O2), and Caspase 8 and 9 levels will be quantified by means of a calorimetric assay.Inhibitory concentrations 50 (IC50) of each drug were obtained in which the cell viability was 50%. The IC 50 found were: cisplatin 20.6μg/mL, AmB 60 μg/mL and derivative AmB 121 μg/mL. When evaluating the morphology of the cells, it is observed that in the treatment with cisplatin at 7μg/mL increased the size of cells. The treatment with AMB and derivative A21 at the same concentration also increased the sizes of cells with more than 1 nucleus were also observed (compared with the control). Cells treated withThe treatment with AmB and the derivative of A21 produced similar alterations in cell morphology than cisplatin. However, the IC50 were different for all treatments evaluated in A549 cells.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of probiotics Bifidobacterium breve and Lactobacillus rhamnosus on inflammation lung in an experimental model of chronic obstructive pulmonary disease
Authors: DE SÁ FIALHO ANA KAROLINA CARVALHO , MIRANDA MUNIQUE TOSTES FERREIRA , CARVALHO JORGE LUIS COSTA , BRITO AURILEIA APARECIDA , ALBERTINI REGIANE , AIMBIRE FLÁVIO 
Published: June 2021

IntroductionChronic pulmonary obstructive disease (COPD) is defined as an abnormal inflammatory response of the lungs to noxious particles or gases, mainly cigarette smoke. Thus, new therapeutic approaches are of unquestionable relevance. Without a specific treatment for COPD patients the use of probiotics via supplementation of diet can be a promising target. This project aims to investigate the beneficial effects of Bifidobacterium breve (Bb) and Lactobacillus rhamnosus (Lr) probiotics in lung inflammatory process in mice in a model of lung emphysema.MethodsThis study was approved by the Ethics Committee of the UNIFESP. The COPD was induced by cigarette smoke inhalation of 14 cigarette per day, twice a day, 7 times/week during 60 days in C57Bl/6 mice. The mice were treated with Lr and Bb at the same time. The pro‐inflammatory mediators as IL‐6, TNF, IL‐1 β, CXCL1, CXCL8, CXCL10, KC, CXCL9, CXCL11 and anti‐inflammatory as IL‐10 in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The expression of mRNA of the MMP9 and MMP12, NF‐κB, STAT3 and TLR 2,4 and 9 in lung were analyzed by quantitative RT‐PCR. The NF‐κB was also analyzed by immunolocalization. The lung tissue was used for histological and morphometric analyzes.ResultsBb and Lr attenuated the cellularity in BALF and reduced the pro‐inflammatory cytokines and inversely increased the anti‐inflammatory. Also, the probiotics reduced the expression of MMP9 and 12, NF‐κB, STAT3 and TLR 2,4 and 9 in lung. Then, the probiotic also changed the airway remodeling (inflammatory infiltrate, alveolar enlargement, collagen, and elastic fibers).ConclusionThis study points out that the probiotics decreased the cellularity on the BALF and the expression of the main transcription factors as a consequence they also reduced pro‐inflammatory cytokines and inversely increase anti‐inflammatory. These results contribute to the understanding of Bb and Lr modulator activities.Support or Funding InformationFinancial Support: Foundation for Research Support of the State of São Paulo (FAPESP)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Probiotics Improve Flora Alternation and Memory Deficits in Aged Mice
Authors: Du Junrong , Yang Xueqin , Yu Dongke , Xue Li 
Published: June 2021

Probiotics, multi‐species live microorganisms, can delay the progression of some neurodegenerative diseases. However, the effects of probiotics on the gut‐brain axis remain unclear, particularly in the context of aging and neurodegenerative diseases. The senescence‐accelerated mouse prone 8 (SAMP8) mouse strain is used as an aging model. To investigate the effects of probiotics, 9‐month‐old male SAMP8 mice were treated with probiotics (four species of Lactobacillus and Bifidobacterium) for 12 weeks. The results demonstrated that probiotics treatment significantly reduced memory deficits, neuronal loss and synaptophysin. 16S RNA analysis revealed that the microbiome composition in the brain and feces was modified by probiotic treatment. In addition, probiotic treatment reduced aging‐induced intestinal barrier and blood‐brain barrier injury. Probiotic treatment also significantly reduced lipopolysaccharide concentrations both in the brain and plasma. Probiotics significantly decreased the immunoreactivity of ionized calcium binding adaptor molecule‐1 and glial fibrillary acidic protein, the expression of Toll‐like receptor 4, the nuclear translocation of nuclear factor‐κB, and mRNA expression of proinflammatory cytokines (tumor necrosis factor‐α and interleukin‐6) in the brain. These findings indicate that the cognitive‐enhancing effects of probiotics in aged SAMP8 mice may be modulated by the gut‐brain axis and the inhibition of inflammation via the LPS‐TLR4/NF‐κB signaling pathway.Support or Funding InformationThis work was supported partly by Sichuan University ‐ Luzhou Project (2016CDLZ‐S16), targeting drug delivery system of Sichuan Province Youth Science and Technology Innovation Team (2016TD0001) and 111 Project of the National Ministry of Education (B18035).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Butyric Acid, a Gut Bacteria‐Produced Metabolite, Decreases Arterial Blood Pressure via a Gut‐Vagus Nerve Signaling in Rats
Authors: Ufnal Marcin , Onyszkiewicz Maksymilian , Gawrys Marta , Huc Tomasz , Aleksandrowicz Marta , Sawicka Aneta , Kozniewska Ewa , Samborowska Emilia 
Published: June 2021

Butyric acid (BA) is one of several short‐chain fatty acids (SCFAs) produced by gut microbiota. The aim of the study was to evaluate if BA may exert hemodynamic effects via an afferent gut‐nervous system signalling. Hemodynamics were recorded in male, 14‐week‐old, anesthetized, Wistar rats. A vehicle (0.9% NaCl), BA, or 3‐hydroxybutyrate, an antagonist of SCFA receptors GPR41/43 (ANT) were administered into the colon (IC) or intravenously (IV). Reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries was tested in vitro. SCFAs concentration was measured using ultra performance liquid chromatograph with mass spectrometer. Physiological BA concentration in the colon content (stools) was ≈ 9mM but 1000‐fold lower in systemic venous blood. The vehicle and ANT did not affect arterial blood pressure (BP) and heart rate (HR). BA administered IC produced 2–3‐fold increase in BA colon content and a prolonged decrease in BP and HR, with no significant changes in QTc, a marker of cardiotoxicity. Intestinal blood flow was not affected. Subphrenic vagotomy and IC pretreatment with ANT significantly reduced the hypotensive effect of IC BA. The hypotensive effect was also reduced by IV administered hexamethonium but not by atropine. BA administered IV produced shorter decrease in BP than BA administered IC, and did not affect HR. The ANT reduced, whereas L‐NAME, a nitric oxide synthase inhibitor, did not affect the hypotensive effect of IV BA. In vitro, BA dilated MA and GMA at concentrations 10–20‐fold higher than physiological concentration of BA in systemic blood. In conclusion, at physiological concentration the colon appears the most likely site of BA action. An increase in colonic BA lowers BP. This seems to be mediated by vagal signaling and GPR41/43.Support or Funding InformationSupported by the National Science Centre, Poland grant no. UMO‐2016/22/E/NZ5/00647This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.