bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of cancer hereditary susceptibility on the prognosis of esophageal cancer patients from high esophageal cancer incidence area in China
Authors: Li Xiumin , Zhao Zhi‐Min , Zhang Yuan‐Zhi , Zhou Fu‐You , Hou Xiao‐Hua , Ji Hong‐Long 
Published: June 2021

ObjectiveTo investigate the impact of hereditary susceptibility on prognosis in patients with esophageal cancer.MethodsA total of 742 cases of esophageal cancer from high risk esophageal cancer regions were followed up successfully. Student's t‐test was used to compare the average age of esophageal cancer onset. Survival curves were plotted by Kaplan‐Meier methods.ResultsThe average onset age in patients with esophageal cancer was not related to the cancer hereditary susceptibility; the survival curve of esophageal cancer cases with positive esophageal cancer family history was significantly higher than negative group (59.83±3.60 VS 37.47±1.95 months, P=0.002); Within both the positive family history of esophageal cancer and malignant tumor groups, cases under 60 years old had significant higher survival rates compared with those of older (P <0.01). In contrast, neither within the negative family history of esophageal cancer nor malignant tumor groups, there was similar difference.ConclusionsEsophageal cancer patients with positive but not negative family history have a better prognosis. Moreover, the younger and middle‐aged patients within both positive family history of esophageal cancer and malignant tumor groups had a better prognosis. These clinical studies indicate that family history and age possess prognostic relevance.
Impaired L‐arginine recycling induces compensatory mechanisms in NO‐dependent vessels
Authors: Chennupati Ramesh , Janssen Ben J.A. , Lamers Wout H , De Mey J.G.R , Koehler SE 
Published: June 2021

IntroductionImpaired endothelial nitric oxide (NO) is a hallmark of endothelial dysfunction. Deficiency of the nitric oxide synthase (NOS) substrate arginine (Arg) may be even more detrimental than NOS deficiency.ObjectiveWe assessed whether impaired Arg recycling inhibited endothelium‐dependent relaxation (EDR).MethodsWe generated endothelium‐selective ASS knockout mice (ASS‐KO) with the loxP/Cre approach, using Tie2Cre for gene ablation. Femoral artery (FA) and saphenous resistance arteries (SRA) were investigated using wire‐myography.ResultsImmunohistochemical stainings on FA and SRA showed specific and complete deletion of ASS in endothelial cells (EC). EDR of FA is dependent on both NO and endothelium‐derived hyperpolarizing factor (EDHF) and was identical in ASS‐KO and WT vessels. In SRA, EDR is NO‐dependent and can be completely blocked by L‐NAME (100μM) in WT vessels. In ASS‐KO vessels, however, L‐NAME inhibits EDR only by 50%.ConclusionReduced arginine recycling in EC of SRA resulted in induction of EDHF‐dependent relaxation in NO‐dependent arteries.
Heterologous sensitization of human AC5: dependence on heterotrimeric G proteins
Authors: Ejendal Karin F K , Sadana Rachna , Vidi Pierre‐Alexandre , Dessauer Carmen W , Watts Val J 
Published: June 2021

We investigated the role of heterotrimeric G proteins in heterologous sensitization of adenylyl cyclase type 5 (AC5). Although acute stimulation of Gαi‐coupled receptors inhibits AC5 activity, persistent receptor activation enhances AC5 activity. This phenomenon is known as heterologous sensitization of AC, and has been implicated in drug dependence.Previous work revealed an absolute requirement for Gαs in heterologous sensitization of AC5. To further elucidate the mechanism, we assessed sensitization in cells devoid of endogenous Gαs, co‐expressing the D2L receptor, AC5, and Gαs mutants. Our data showed that AC5‐Gαs, but not Gβγ‐Gαs interactions or palmitoylation of Gαs, were required for heterologous sensitization of AC5.Next, we explored the role of Gβγ‐AC5 interactions in heterologous sensitization. Sequestering Gβγ with βARK‐ct partially attenuated heterologous sensitization. Deletion of a novel N‐terminal Gβγ interacting domain of AC5 abolishes Gβγ binding, but does not greatly alter other forms of acute regulation. However, the AC5 deletion mutant was selectively impaired in heterologous sensitization. Together, these studies support a complex model of heterologous sensitization of AC5 where Gαs is directly interacting with AC5. In contrast, Gβγ appears to have multiple and indirect roles in heterologous sensitization of AC5.Supported by P.U. and grants VJW‐MH060397 and CWD‐GM060419.
Effect of Resveratrol and Curcumin on Tumor Volume and Survival in Ehrlich Ascites Carcinoma‐Bearing Mice
Authors: El‐Azab Mona Farag , Hishe Hailemichael , Moustafa Yasser , El‐Awady El‐Sayed 
Published: June 2021

Solid tumors were induced by a subcutaneous injection of Ehrlich ascites carcinoma (EAC) cells (2.5x106 cells/mouse) in the right flank of Swiss albino mice. These tumors were used to evaluate the antitumor effect of resveratrol (10mg/kg, i.p), or curcumin (10mM, 100μl/mouse, i.p.) as individual treatments or in combination with carboplatin (5mg/kg, i.p). Tumor size was measured every other day for 21 days. Mortality was recorded daily along the study period to calculate the percentage survival of animals, mean survival time (MST) and percentage increased life span (%ILS). Individual treatments with resveratrol or curcumin produced a significant reduction (p≤0.05) in tumor volume, which tended to be enhanced progressively from the individual treatments to the combinations with carboplatin. The treatment with carboplatin, curcumin and their combination could expand the life span of animals for 78, 107 and 105 days respectively. The combination of curcumin with carboplatin could produce the highest increase in MST (68.20±6.70) and %ILS (82.4%). Single and combined treatment of resveratrol produced an enhancement of the life span by 34% and 57.2%, respectively.These data show that resveratrol and curcumin produced antitumor effect on EAC solid tumor in Swiss mice. The results suggest the beneficial role of the phytochemicals as adjuvants to chemotherapy in the treatment and/or prevention of cancer.
Aerobic Exercise Enhances The Muscle Protein Anabolic Effect Of A Mixed Meal In Older Adults
Authors: Timmerman Kyle L. , Dhanani Shaheen , Glynn Erin L. , Fry Christopher S. , Drummond Micah J. , Rasmussen Blake B. , Volpi Elena 
Published: June 2021

Muscle protein metabolism is resistant to the anabolic effects of mixed feeding and insulin in older adults. Aerobic exercise improves insulin sensitivity of muscle proteins in elders. We tested if an acute bout of aerobic exercise can also overcome the anabolic resistance to a mixed meal in healthy, sedentary older subjects (age: 70±3 yr).Using a randomized cross‐over design, we measured blood flow and muscle protein kinetics (13C6‐phenylalanine) at baseline and during mixed meal ingestion (20g of essential amino acids + 35g of glucose) on 2 occasions: after rest (CTRL) or after a bout of aerobic exercise (EX). We report preliminary data from 4 subjects. Blood flow (CTRL, basal: 2.09±0.49, meal: 2.52±0.88; EX, basal: 2.47±0.46, meal: 4.06±1.06 ml/min/100 ml leg) and mixed muscle protein synthesis (CTRL, basal: 0.054±0.008, meal: 0.053±0.006; EX, basal: 0.057±0.005, meal: 0.079±0.007 %/h) increased (P<0.05) from baseline during mixed meal ingestion only in EX but not in CTRL. Phenylalanine delivery to the leg increased significantly (P<0.05) in both conditions (CTRL, basal: 137±29, meal: 422±137; EX, basal: 142±17, meal: 714±123, nmol/min/100 ml leg), but the change was larger (P<0.05) in EX.In conclusion, these preliminary data suggest that a prior bout of aerobic exercise restores the anabolic effects of a mixed meal in older adults. This effect may be partially due to increased blood flow and amino acid delivery.Supported by NIA R01 AG018311 and P30 AG024832
The α2 isoform of the Na, K‐pump is involved in synchronization of smooth muscle cells in the arterial wall.
Authors: Aalkjær Christian , Møller‐Nielsen Nina , Matchkov Vladimir 
Published: June 2021

We have hypothesized that the ouabain‐sensitive Na, K‐pump can regulate smooth muscle gap junction function. To test this hypothesis and determine the relevant isoform we investigated the effect of downregulation of the α2 isoform of Na, K‐pump.We transfected cultured smooth muscle cells (SMCs) and rat small mesenteric arteries with siRNA against the α2 isoform of Na, K‐pump and with eGFP siRNA, as a control. Paired SMCs were used as a model for electrical coupling by measuring membrane capacitance and synchronized SMC activity was assessed by measuring isometric force.Pairs of SMCs had a capacitance of 90.4±9.4pF, n=7 twice that of single cells. SMCs were uncoupled when the Na, K‐pump was inhibited by 10 μM ouabain (46.1±7.2pF). β‐glycyrrhetinic acid (βGA) had no additive effect (41.9±4.9pF). Downregulation of the α2 Na, K‐pump significantly reduced the capacitance of cell pairs (33.4±4.1pF) and made them insensitive to ouabain (34.1±4.2pF). βGA uncoupled residual coupling (28.3±3.0pF). Arteries downregulated for the Na, K‐pump had significant reduced amplitude of noradrenalin‐induced vasomotion. This is consistent with the suggested role of gap junction for synchronization of SMCs in the vascular wall.We demonstrate the importance of α2 isofom of the Na, K‐pump for intercellular coupling in the vascular wall and its involvement in the regulation of vasomotion.
Key role of Ca2+‐activated K+ channels of small and intermediate conductance in the NO signaling of resistance vessels
Authors: Gaete Pablo S , Figueroa Xavier F 
Published: June 2021

Ca2+‐activated K+ channels (KCa) and nitric oxide (NO) play a central role in the control of vasomotor tone in resistance arteries. To evaluate the contribution of KCa channels to NO‐mediated dilation, we analyzed the vasomotor responses and NO production (chemiluminiscence) induced by the endothelium‐dependent vasodilator, acetylcholine (ACh), or the Ca2+ ionophore, ionomycin, in isolated arterial mesenteric bed of rat. ACh (0.01–10μM) elicited a concentration‐dependent vasodilatation. In phenylephrine‐contracted mesenteries, NO synthase (NOS) inhibition with Nω‐nitro‐L‐arginine (L‐NA) reduced the response to ACh. Blockade of KCa channels with tetraethylammonium (TEA) or inward rectifier K+ channels with Ba2+ blunted the response to ACh. L‐NA inhibited the ACh‐induced relaxation in presence of Ba2+, but not TEA. In addition, TEA blocked the NO production induced by ACh. In KCl‐contracted vessels, the relaxation‐elicited by ACh or 1μM ionomycin was abolished by L‐NA and inhibited by TEA or simultaneous blockade of KCa channels of small (SKCa) and intermediate (IKCa) conductance with apamin and TRAM‐34, respectively. Apamin and TRAM‐34 also abolished the NO production activated by 100nM ACh. These results indicate that functional SKCa and IKCa channels are required for Ca2+‐mediated eNOS activation. Membrane hyperpolarization is not involved in the regulation of NO production by these channels.VRAID 15/2009
The ZDSD, a New Rat Model of Metabolic Syndrome: Evidence of Cardiovascular Disease
Authors: Packer C Subah , Meulen Leeanna M , Boice Alexa M , Coy Kathy , Peterson Richard G 
Published: June 2021

A new rat model, the ZDSD, has an intact leptin system while having typical metabolic syndrome biomarkers. The goal was to determine if ZDSD also suffer from cardiovascular disease typical of metabolic syndrome. ZDSD and control SD blood pressures (BP) were monitored for several weeks. Right ventricular to left ventricular plus septum weight ratios, RV/(LV+S), were measured. None of the 6 ZDSD had high systemic BP. Two ZDSD developed systemic hypotension that correlated with severe diabetes and weight loss. ZDSD RV/(LV+S) tended to be higher than SD RV/(LV+S) indicative of RV hypertrophy and pulmonary hypertension. Results suggest that the severely diabetic ZDSD were in end stage congestive heart failure (CHF) resulting from a particularly malignant form of metabolic syndrome. A younger cohort of less severely diabetic ZDSD need to be studied in order to know if systemic hypertension plays a role in development of CHF in this model of metabolic syndrome.Supported by PreClinOmics. L Meulen and A Boice were 2009 Indy Project SEED Scholars supported by American Chemical Society (ACS), Lilly, DowAgroSciences, IUPUI Indiana Clinical and Translational Sciences Institute (CTSI)
Agmatine‐mediated rat mesenteric artery relaxation via NO synthesis
Authors: Gadkari Tushar , Acosta Zenith , Tsoukias Nikolaos , Joshi Mahesh S 
Published: June 2021

AimTo determine membrane receptor‐dependent or independent mechanisms of agmatine (decarboxylated arginine) relaxation of rat mesenteric arteries.BackgroundIn spite of excess levels of intracellular L‐arginine, exogenous L‐arginine still activates cellular synthesis of nitric oxide (NO) in a phenomenon called “arginine paradox”. Our previously published data (PNAS, 104, 9982, 2007) show that L‐arginine or agmatine may be initiating the NO synthesis via receptor binding and release of intracellular Ca+2 in endothelial cells. Here we have tested the same mechanism in isolated rat mesenteric arteries.MethodsThe individual 2nd order mesenteric arteriolar segments from rats (250–300 g male, Sprague‐Dawley) were cannulated at both ends in a vessel chamber that was continuously perfused intraluminally and pre‐constricted with norepinephrine (2 μM) in modified Krebs buffer at 37°C. For internal diameter measurements, the vessel chamber was mounted on the stage of a microscope fitted with a video camera leading to video caliper. Mounted vessels were allowed to stabilize for 60 min before initiating experiment.ResultsThe data show that agmatine completely relaxed the vessel with an EC50 of 58.75 ± 12.1 μM (n=4) and this relaxation could be significantly inhibited with nitric oxide synthase inhibitor, L‐NAME (0.5 mM) with EC50 of 315 μM (n=1).ConclusionAgmatine dose‐dependently relaxed the rat mesenteric artery and NO mediated the relaxation process.This work was supported in part by NIH grant SC1HL095101
L‐arginine intake improves tolerance to physical exercise and vascular reactivity in obese trained rats
Authors: Zanesco Angelina , Rojas‐Moscoso Julio , Gómez‐Campos Rossana , da Silva Carmem Valgas , Carneiro Everardo , Antunes Edson , Priviero Fernanda B. M. 
Published: June 2021

We assessed the effect of L‐Arg ingestion on tolerance to exercise (EX) and vascular reactivity of rats fed with a hyperlipidic diet (HD) and submitted to EX. Male Wistar rats were divided in sedentary (SD), exercised (EX), SD + L‐Arg (SDLA) and EX + LArg (EXLA). After 4 weeks of HD intake, rats underwent to supplementation and an EX program of running for further 4 weeks. Tolerance to exercise was tested until exhaustion. Concentration‐response curves for acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PE) were obtained in mesenteric artery (RMA). Plasma MDA and SOD levels were measured. Body weight gain was reduced in EX (30 ± 8 g) and SDLA (Δ: 49 ± 6 g) compared to SD (Δ: 90 ± 11 g). A further reduction was found in EXLA (22 ± 8 g). Tolerance to exercise was higher in EX (15 ± 1 min) compared to SD (7 ± 1 min). L‐Arg raised tolerance to exercise in EXLA (20 ± 2 min) and SDLA (11 ± 1 min). In RMA, L‐Arg increased the potency (pEC50) of ACh in EXLA (7.89 ± 0.07) and SDLA (8.14 ± 0.04), compared to SD (7.65 ± 0.04) as well as the pEC50 of SNP in EXLA (8.07 ± 0.11 vs 7.57 ± 0.13 in EX). Responses to PE were not altered. Neither SOD activity nor MDA levels were altered by L‐Arg or exercise. In conclusion, L‐Arg increased body weight loss and tolerance to exercise in SD and EX. In addition, L‐Arg improved relaxation in RMA of EXLA which was not associated with changes in the redox state.Financial Support: FAPESP
Vascular relaxation by ethanol extract of Xanthoceras sorbifolia via Akt‐ and SOCE‐eNOS‐cGMP signaling
Authors: Jin Song Nan , Wen Jin Fu , Li Xiang , Kang Dae Gill , Lee Ho Sub , Cho Kyung Woo 
Published: June 2021

ObjectiveXanthoceras sorbifolia Bunge has long been used as a folk medicine in China. The purpose of the present study was to define the effects of ethanol extract of leaves of X. sorbifolia (EXS) on the vascular tone and the mechanisms by which EXS relaxes vascular smooth muscle in isolated rat aortic rings.Methods and ResultsExperiments were performed in isolated rat aortic rings. Aortic ring was suspended in organ bath and isometric tension was recorded in response to drugs. EXS (0.1–100 ug/ml) produced concentration‐dependent relaxation of aortic rings precontracted with phenylephrine. Endothelium‐denudation abolished the EXS‐induced vasorelaxation. L‐NAME and ODQ blocked the EXS‐induced vasorelaxation. Diltiazem had no effect on the EXS‐induced vasorelaxation. However, Ca2+ ‐free buffer attenuated the EXS‐induced vasorelaxation. Thapsigargin, 2‐APB, and Gd3+, modulators of store‐operated Ca2+ entry (SOCE), and Wortmannin, an inhibitor of Akt, significantly attenuated the EXS‐induced vasorelaxation. However, indomethacin, atropine, and propranolol had no effect on the EXS‐induced vasorelaxation. EXS increased cGMP levels of the aortic rings in a concentration‐dependent manner.ConclusionThese data demonstrate that EXS relaxes vascular smooth muscle via endothelium‐dependent Akt‐ and SOCE‐eNOS‐cGMP signaling pathways. Supported by NSFC (No30570669; 30971080).
Alteration of guanylyl cyclase‐activated vasorelaxation in thoracic aorta from hyperthyroid rats
Authors: Wen Jin Fu , Jin Song Nan , Wang Yan Li , Zhou Guang Hai , Wang Xin Nong , Cho Kyung Woo 
Published: June 2021

ObjectiveNitric oxide (NO) and C‐type natriuretic peptide (CNP) activate soluble (sGC) and particulate guanylyl cyclas e (pGC), respectively, and play important roles in the mainte nance of cardiovascular homeostasis. The purpose of the present study was to define the alteration of pGC‐ and sGC‐ac tivated vasorelaxation in the thoracic aorta from hyperthyroid rats.Methods and ResultsHyperthyroidism was induced by administering L‐thyroxine (T4, 0.05 mg/100 g, sc) daily for 16 days. Experiments were performed in isolated rat aortic rings. CNP (0.1–1000 nM) and SNAP (10‐10000 nM) induced vascular relaxation in a concentration‐dependent manner in aortic rings from eu‐and hyperthyroid rats. The responses were significantly attenuated in aortic rings from hyperthyroid rats. ODQ (10 uM), an inhibitor of sGC, blocked the SNAP ‐induced vasorelaxation of aortic rings from both eu‐ and hyperthyroid d rat. To define the changes in response to cGMP, 8‐Br‐Cgmp (1–100 uM), a cell‐permeable cGMP analog, was used. 8‐Br‐cGMP‐induced vasorelaxation was attenuated in aortic rings from hyperthyroid rats compared to those from euthyroid rats.ConclusionsThese data demonstrate that pGC‐ and sGC‐activated vaso relaxation is attenuated in thoracic aorta from hyperthyroid rats which may be a part of the pathophysiology of the disease. Supported by NSFC (No30570669; 30971080).
Influence of myostatin on skeletal muscle plasticity
Authors: Reisz‐Porszasz Suzanne , Abraham Andrea , Baker Michael , Kovanecz Istvan , Porszasz Janos , Caiozzo Vincent J. 
Published: June 2021

The objective of this study was to investigate myostatin (Mst) role in the process of muscle structural and functional changes in adult skeletal muscle. Myostatin (growth and differentiation factor‐8, GDF‐8) regulates skeletal muscle growth and differentiation during embryogenesis, but its function in adult muscle is not understood. Three genetically altered animal (6 month old) models were used for bilateral compensatory overload experiment: Mst‐null (KO) mice, Mst overexpressing transgenic (TG) and conditional Mst overexpressing transgenic (CMOT, first time reported) compared with wild type (WT) males (five animals/group). Plantaris muscles were analyzed for contractile measurement, morphometry, histochemistry and gene expression profile. Plantaris muscle weight increased in all groups, but biggest increase was found in CMOT (200%) and the smallest was in KO (158%) mice. The same tendency was observed in total plantaris muscle cross sectional area changes. Fiber transition from oxidative to glycolytic fiber was identified in each group with the highest rate in KO (17%). Fiber number increased after overload indicating that Mst does not inhibits cell proliferation in adult muscle. We conclude that Mst plays a different role in muscle during adulthood regulating muscle structure, composition, and physical performance.This study was supported by 1R21AR054101, G12RR030262, and P20MD000545 grants.
Physical Activity and the Incidence of Acute Mountain Sickness in United States Antarctic Program Participants Following Rapid Transport to the South Pole: Antarctic Study of Altitude Physiology (ASAP)
Authors: Ceridon M L , Anderson P J , Miller A D , Beck K C , OMalley K A , Johnson J B , Johnson B D 
Published: June 2021

BackgroundPhysical activity has been proposed as a risk factor for altitude illness however it is unclear whether the total amount or intensity of activity determines illness.PurposeTo examine activity patterns relative to the incidence of acute mountain sickness (AMS) in United States Antarctic Program workers rapidly transported to the South Pole (SP, 9303 ft).Methods53 medically screened subjects (age=37±10yr, BMI=24±3 kg/m2) were transported by a 3 hour flight from McMurdo Station (sea level, SL) to the SP. Physical activity was monitored at SL and for 3 days after ascent using BodyMedia® activity monitors. Symptoms of AMS were assessed using Lake Louise Questionnaires.Results53% of subjects displayed AMS between SP days 1–3 (23% day 1, 43% day 2, 15% day 3). Energy expenditure at SP was 3414±944, 3458±781, & 3543±869 Calories/day for days 1–3, respectively. Steps/day at SP was 12593±4926, 13124±4392, & 12966±4482 for days 1–3, respectively. Overall, more activity at higher intensity (>3 METS) on SP day 1 was associated with higher AMS incidence the next morning (p<0.05). Also, calorie expenditure with activity at >3 METS and time of activity at >6 METS in the first 24 hours after ascent independently increased the odds of AMS on SP day 2 (p<0.05).ConclusionsWith rapid transport to altitude, moderate to intense activity within the first 24 hours of ascent contributes to the incidence of AMS. NSF ANT 0540710
Monocyte Chemoattractant Protein‐1 (MCP‐1) released from alveolar macrophages mediates the systemic inflammation of alveolar hypoxia
Authors: Chao Jie , Donham Paula , Wood John G , Gonzalez Norberto C 
Published: June 2021

Alveolar hypoxia (AH) produces widespread systemic inflammation in rats. The inflammation is initiated by a circulating mediator released from alveolar macrophages (AMØ) activated by the low alveolar PO2. The mediator(s) induces mast cell degranulation (MCD) with release of inflammatory agents. Recent data suggest MCP‐1 as a mediator. If this is true: 1) Circulating levels of MCP‐1 should increase with AH in intact rats; 2) AMØ depletion should prevent this increase; 3) Plasma from intact AH rats, but not AMØ‐depleted AH rats, should produce MCD; 4) MCP‐1 added to normoxic plasma or AMØ supernatant should produce MCD.AH (FIO2 = 0.1 for 60 min) produced a rapid (5 min) and sustained 6‐fold increase in plasma MCP‐1 of intact rats. 2) This increase was abolished by AMØ depletion by tracheal instillation of clodronate‐containing liposomes. 3) Mast cell immersion in plasma from AH intact rats, but not in plasma from AMO‐depleted rats, produced MCD. 4) Dose‐dependent MCD occurred when MCP‐1 was added to normoxic AMØ supernatant or rat plasma, but not when added to normoxic culture medium.ConclusionsIn the intact, conscious rat, AH induces release of MCP‐1 from AMØ, which, in turn, produces MCD and initiates systemic inflammation of AH. To induce MCD, MCP‐1 requires another substance(s) which is present in both normoxic plasma and normoxic AMØ supernatant.Supported by NIH HL39443‐18, AHA 0815652G and APS Frontiers in Biology