bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saikosaponin‐b2 inhibits tumor growth and inflammation of hepatocellular carcinoma by regulating STK4 / IRAK1 / NF‐κB signaling in H22 tumor‐bearing mice
Authors: Gao Zi‐Han , Li Rui‐Fang , Lv Xing‐Zhi , Wang Hong‐Wei , Li San‐Qiang , Wang Jian‐Gang 
Published: June 2021

The tumor suppressor serine/threonine‐protein kinase 4 (STK4) may regulate inflammatory signaling in macrophages and thereby protective against inflammation‐associated HCC. Saikosaponin (SS)‐b2, a major bioactive ingredient of saikosaponins from Chinese thorowax root, exhibited anti‐cancer, anti‐inflammatory, anti‐viral, and anti‐oxidant activity. However, the anti‐tumor effect and its signaling mechanism of SS‐b2 on H22 hepatocellular carcinoma remain unknown. This study investigated the anti‐tumor effect of SS‐b2 on H22 hepatocellular carcinoma by regulating STK4/IL‐1 receptor associated kinase 1(IRAK1)/NF‐κB signaling. BALB/c mice were randomly divided into model group (normal saline, 10mL·kg−1·d−1, i.p.), different dose SS‐b2 group (3, 6, 12 mg·kg−1·d−1, i.p.) and doxorubicin group (DOX, 2 mg·kg−1, once every other day, i.p.). The mice were administered for 10 days. The results showed that SS‐b2 had a significant anti‐tumor effect on H22 xenograft mice. The tumor inhibiory rate of SS‐b2 was 16.8%, 32.7% and 55.8% respectively at 3 mg·kg−1, 6 mg·kg−1 and 12 mg·kg−1 dose. SS‐b2 decreased the spleen index in a dose‐independence way but it decreased the liver index only at 12 mg·kg−1 dose. SS‐b2 also significantly reduced the levels of AST and ALT in serum at 6 mg·kg−1 and 12 mg·kg−1. HE Staining revealed that SS‐b2 significantly attenuated the pathological morphology changes. Tumor tissue showed large necrotic, nucleus lysis and vacuole areas in mice with SS‐b2 treatment. Immunohistochemistry results showed that the positive expression of STK4 protein in tumor tissue increased however IRAK1 protein expression decrease significantly in SS‐b2 groups compared with the model group. Moreover, Western blot analysis also showed that the protein expression of STK4 increased whereas the expressions of IRAK1 and NF‐κB protein were decreased in tumor tissue, spleen, and serum in SS‐b2 treatment group. These results suggest that SS‐b2 exerts a significant anti‐tumor effect on H22 xenograft mice by regulating STK4/IRAK1/NF‐κB pathway.Support or Funding InformationThis study was supported by Science and Technology Key Research Fund funded projects of Henan Province, China (No. 142102310137), the Science and Technology Development Project of Luoyang City (No. 1603001A‐3).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
PDE1 Inhibition Attenuates Doxorubicin‐Induced Toxicity in Primary Mouse Cardiomyocytes
Authors: Vigneshwar Navin , Samidurai Arun , Movsesian Matthew , Das Anindita , Kukreja Rakesh C 
Published: June 2021

BackgroundDoxorubicin (DOX) is a widely used and effective chemotherapeutic agent, but is associated with a delayed and progressive cardiomyopathy. Phosphodiesterase 5 (PDE5) inhibitors have been shown to be protective of heart function with DOX co‐treatment in animal models, but PDE5 is expressed at low levels in human heart. In contrast, phosphodiesterase 1 (PDE1) comprises a large fraction of the cGMP‐hydrolytic activity in both human and mouse heart. We hypothesized that PDE1 inhibition would be protect against DOX cardiotoxicity by improving cell survival (cGMP effect) and eliciting inotropic response (a cAMP effect).Methods and ResultsIsolated cardiomyocytes from adult male C57BL/6J mouse were treated with DOX (1 μM) and/or a quinazoline‐based PDE1‐selective inhibitor (5 μM) for 24 hours. Necrosis and apoptosis were assessed by trypan blue staining and TUNEL assay, respectively. Mitochondrial membrane potential (ΔΨm) was evaluated by JC‐1 staining. DOX treatment increased cardiomyocyte necrosis, apoptosis and caused loss of ΔΨm. Treatment with PDE1 inhibitor in combination with DOX significantly (P<0.05) reduced necrosis (37.4±3.9 vs 60.2±4.1% DOX alone, n=6; Figure 1A), apoptosis (17.3±1.22 vs 39.6±2.4% DOX alone, n=8; Figure 1B) and improved ΔΨm (3.1±0.4 vs 0.98±0.01 with DOX alone, n=4; Figure 1C).ConclusionPDE1 inhibition has anti‐apoptotic and anti‐necrotic effects against DOX‐induced cardiomyocyte death. PDE1 inhibition in combination with DOX could potentially be an efficient therapeutic strategy to reduce DOX‐induced cardiotoxicity in cancer patients.Support or Funding InformationR37HL0510454This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Novel Functional Role of TASK‐1 in Hypoxia
Authors: Yu Yang , He Harrison , Hu Keli 
Published: June 2021

TASK‐1, a member of the two‐pore domain potassium channel family, is strongly expressed in the heart. However, little is known about the regulation and function of cardiac TASK‐1 channels. The present study was designed to explore whether cardiac TASK‐1 channels play an essential role in the cytoprotection against hypoxia and reoxygenation. A cellular model of hypoxia or hypoxia and oxygenation from rat heart‐derived H9c2 cells and HEK293T cells was employed. The advantage of using HEK293T cells is that they lack endogenous TASK‐1. Hypoxia was induced by incubating cells in an airtight chamber in which O2 was replaced by 95% N2 and 5% CO2 with the glucose‐free Tyrode solution. Trypan blue cell viability assay was utilized in combination with biochemical analysis and immunofluorescence microscopy. The cell viability assay revealed that TASK‐1 expression increased the number of viable cells in HEK293T cells subjected to 2 hours of hypoxia followed by 2 hours of reoxygenation (H/R). To dissect the protective role of TASK‐1, mitochondrial membrane potential (MMP) was assessed by tetramethylrhodamine (TMRE) fluorescence. Our data indicated that MMP was significantly decreased by H/R, but was maintained by TASK‐1 expression. Our work on the subcellular localization of TASK‐1 demonstrated that while TASK‐1 showed a strong plasma membrane localization, a small fraction of TASK‐1 colocalized with the mitochondrial marker MitoTracker in intact cells and/or isolated mitochondria. H/R decreased the expression of TASK‐1 along cell periphery but did not alter colocalization of TASK‐1 with MitoTracker in HEK293T cells and/or H9c2 cells. Western blot analysis further supported the notion that the total cellular TASK‐1 expression from H9c2 cells was significantly reduced by H/R. Moreover, our data showed that Cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (mPTP), prevented reduction in MMP by H/R, the effect was not further enhanced by expressing TASK‐1. In summary, we provided the evidence that TASK‐1 channels are protective against hypoxia and reoxygenation‐induced injury, possibly by their capacity of maintaining the mitochondrial membrane potential via inhibiting mPTP opening.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal Effects Induced by Two Phospholipase A2 (Asp‐49 and Lys‐49) Isolated from Bothropoides pauloensis Snake Venom
Authors: Marinho Aline Diogo , Jorge Antonio Rafael Coelho , Filho Adriano Jose Maia Chaves , Junior Francisco Assis Nogueira , Monteiro Helena Serra Azul 
Published: June 2021

Acute renal failure (ARF) wich is one of the most serious complications of Bothrops snakebites, is one of the main causes of death and consequences for victims. However, its pathogenesis remains unclear. Considering that isolated toxins are relevant tools for understanding the actions of the whole venom, we studied properties of phospholipases A2 (Asp‐49 and Lys‐49) isolated from Bothrops pauloensis (from State of São Paulo, Southeast region of Brazil), on isolated perfused kidney of rat. The control group perfused with modified Krebs–Henseleit solution alone. The PLA2s (3μg/mL) caused significant effects in isolated rat kidney, Asp‐49 reducing perfusion pressure(PP), the Renal Vascular Resistence (RVR), the Urinary Flow (UF), the Glomerular Filtration Rate (GFR) and the percentage of tubular sodium (%TNa+), chloride (%TCl−) and potassium (%TK+). The Lys‐49 increased PP and UF and decreased the RFG and the %TNa+, %TK+ and %TCl‐. Oxidative stress in kidney tissue was evaluated by TBARS (thiobarbituric acid reactive substances), Nitrite and reduced Glutathione (GSH) level measurement. A significant increase was observed in TBARS (Lys‐49) and Nitrito (Asp‐49 and Lys‐49) and a decrease in GSH levels (Asp‐49) and increase (Lys‐49). The levels of inflammatory cytokines were measured. We analized the inflammatory cytokines, pro‐inflammatory interleukin 1 (IL‐1), tumor necrosis factor‐α (TNF‐α) and anti‐inflammatory interleukin 10 (IL‐10). The results showed high levels of both cytokines (by Lys‐49) and incresed TNF‐α and IL‐10 by Asp‐49. Increased TBARS, Nitrito level and decreased of GSH activity might be implicated in the presence of oxidative stress in patients with snake bite envenomation. These findings demonstrated that PLA2s caused nephrotoxicity in isolated kidney. The characterization of the effects in the isolated kidney gives strong evidences that the acute renal failure induced by these PLA2s is a result of the direct nephrotoxicity which may involve oxidative and inflammatory mechanisms.Support or Funding InformationCAPES, CNPq, UFC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Muscadine Grape Extract Treatment Improves Aortic Pulse Wave Velocity and Superior Mesenteric Artery Pulsatility Index in Hypertensive Transgenic (mRen2)27 Female Rats
Authors: Ryalat Fatima , Cruz‐Diaz N , Tallant EA , Gallagher PE , Diz Di , Yamaleyeva LM 
Published: June 2021

Hypertension is a major risk factor for heart disease and stroke, the leading causes of death in the United States. Hypertension is characterized by changes in vascular hemodynamics including vascular stiffness of the elastic conduit arteries and increased peripheral vascular resistance of the smaller muscular arteries that are associated with tissue damage. Dietary phenolic compounds are linked to beneficial cardiovascular effects. In this study, we investigated the influence of a muscadine grape extract (MGE; Piedmont Research & Development Corp.) on arterial stiffness and peripheral vascular resistance in hypertensive transgenic (mRen2)27 rats. We also investigated whether sex modulates MGE effects on arterial dysfunction in this rat model. MGE was administered in drinking water (0.2 mg polyphenolics/mL) starting at the age of 14 weeks, control animals were given regular water (n = 5 in each group, control and MGE‐treated female; n = 4 in each group, control and MGE‐treated male). After 6 weeks of treatment, noninvasive cardiovascular hemodynamic measurements were performed using a preclinical ultrasound system, Vevo LAZR (Fujifilm, Visual Sonics). Systolic blood pressure was measured using tail cuff plethysmography (NIBP‐8, Columbus instruments, Ohio). Aortic arch pulse wave velocity (PWV) was used as a measure of arterial stiffness and superior mesenteric artery (SMA) pulsatility index (PI), defined as PI = [(peak systolic velocity‐ end diastolic velocity)/mean flow velocity] was used as an indicator of peripheral vascular resistance. (mRen2)27 rats treated with MGE had lower aortic arch PWV compared with controls in both male (2.31 ± 0.33 vs. 3.79 ± 0.37 m/s, p < 0.05) and female (2.44 ± 0.13 vs. 3.62 ± 0.37 m/s, p < 0.05) rats. In addition, MGE‐treated female rats had lower SMA PI than control females (0.97 ± 0.07 vs. 1.27 ± 0.10, p < 0.05). There were no significant effects of the extract on SMA PI in males (1.19 ± 0.05 vs. 1.34 ± 0.07). These MGE effects were independent of changes in body weight (508 ± 3 vs. 493 ± 9 g in males, 282 ± 5 vs. 280 ± 5 g in females), cardiac index (4.5 ± 0.1 vs. 4.6 ± 0.3 mg/g in males, 4.9 ± 0.3 vs. 4.5 ± 0.2 mg/g in females), systolic blood pressure (188 ± 5 vs. 199 ± 4 mm Hg in males, 191 ± 12 vs. 194 ± 12 mm Hg in females) or cardiac function. In conclusion, six weeks of MGE treatment improved arterial stiffness in both male and female hypertensive rats. More pronounced beneficial vascular effects in females suggest that MGE actions in the arterial vasculature are modulated by sex.Support or Funding InformationChronic Disease Fund Research.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Melatonin attenuates bisphenol A‐induced alterations in the cardio‐renal system of rats through the antioxidant defense mechanism
Authors: Ola‐Davies Olufunke Eunice , Olukole Samuel Gbadebo , Oyagbemi Ademola Adetokunbo , Omobowale Temidayo Olutayo , Olaogun Sunday Charles , Adedokun Rahmon Akinyele , Oke Bankole Olusiji 
Published: June 2021

Bisphenol A (BPA), an endocrine disrupting chemical (EDC) used in the production of plastics and epoxy resins has been incriminated in a number of biological dysfunctions while melatonin (MLT) is a known antioxidant capable of ameliorating EDC‐induced perturbations. Although limited number of studies exist on the effect of BPA on the cardio‐renal system, there is the dearth of research information on the effect of MLT on rats exposed to environmentally relevant doses of BPA. This study was therefore designed to investigate the effects of MLT on BPA‐induced alterations in the cardio‐renal system of rats. Gravid rats were randomly assigned into five groups (n=5): Group 1 (control) received 0.2 mL 1% dimethyl sulfoxide (DMSO)/99% canola oil as vehicle; Group 2 received BPA at 25 μg/kg/day; Group 3 received BPA at 250 μg/kg/day; Group 4 received BPA at 25 μg/kg/day with concurrent MLT 1 mg/kg/day; and Group 5 received BPA at 250 μg/kg/day with concurrent MLT 1 mg/kg/day. All treatments were administered by gavage from gestational day (GD) 10–21. Thereafter, three male offspring randomly from each litter per group (n=15) were weighed; blood pressure parameters and electrocardiogram taken on post‐natal day (PND) 120. The heart and kidney samples were harvested for markers of oxidative stress and antioxidant defense system, histopathology and histochemistry using standard methods. BPA induced a significant increase in heart rate but significantly decrease systolic, diastolic and mean arterial blood pressure. Exposure to BPA caused significant decrease in P wave interval, PR duration, R wave amplitude and QT interval but significant increase in QRS duration. Also, BPA significantly elevated both cardiac and renal MDA, H2O2, GSH and GPx. Cardiac and renal lesions induced by BPA included erosion of epithelial cells, congestion of blood vessels as well as necrosis. Moreover, BPA induced a significant reduction in cardiac and renal polysaccharide activities. However, the concomitant treatment with MLT attenuated all the observed BPA‐induced alterations of the cardio‐renal system. Hence, MLT attenuates alterations induced by environmentally relevant doses of BPA in the cardio‐renal system.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Ramadan Fasting on Arginase Activity in Healthy Volunteers
Authors: Shatanawi Alia , Gharaibeh Ahmad M , Gharaibeh Munir N 
Published: June 2021

The practice of fasting is performed by many communities for religious or spiritual reasons. Additionally, in the recent years many health benefits were associated with different kinds of fasting. These include: controlling blood glucose levels , reducing insulin resistance, reducing inflammation, improve heart health, lowering blood pressure and boosting brain function while prevent neurodegenerative disorders. Moreover, there is proven evidence on the effects of Ramadan fasting, performed by muslims for one month, on improving vascular health, blood flow and enhancing endothelial function in patients with cardiovascular disease. Fasting was reported to increase nitric oxide (NO) levels and decrease asymmetric dimethylarginine (ADMA); a novel cardiovascular risk factor. Nitric oxide, a potent vasodilator and vascular protective molecule, is produced by endothelial cells by the action of endothelial nitric oxide synthase (eNOS) on L‐arginine. Arginase, an enzyme implicated in many cardiovascular diseases, can compete with eNOS for their common substrate, L‐arginine to produce urea and ornithine. We and others have reported the effects of arginase inhibition on improving endothelial function and NO levels in different cardiovascular diseases and in diabetes.Our project aims to study the effect of Ramadan fasting on arginase activity in healthy individuals. We measured arginase activity one day before the start of fasting and on the last day of fasting for thirteen young male adults, ages between 18–35 years old. The fasting performed is to withhold from eating, drinking and smoking from sunrise to sunset (about 15 hours) everyday for a period of one month. Plasma arginase activity is measured using a colorimetric reaction of urea production. Our results show a modest though significant decrease in arginase activity of 15.7 ± 4.2%. We also determined basal urea levels and observed no change in these levels. Our results propose one important benefit of fasting through lowering arginase activity thus reserving available L‐arginine for NOS and increasing NO levels. We also noted that basal urea levels did not change. It was expected that not drinking water for long hours could increase chances of dehydration which can increase plasma urea concentrations, but this did not occur. In conclusion, our result show another added health benefit of fasting to the vascular system which is lowering arginase activity. Fasting under doctor supervision can be used in selected patients with vascular diseases to maintain and promote NO levels. We yet have to determine the effects of fasting on other systems of the body such as liver and kidney to preclude any deleterious side effects of this practice.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 Diminazene aceturate treatment on some cardiovascular parameters and antioxidant status of apparently healthy horses
Authors: Omoniwa David , Ogunpolu Blessing , Omoniwa Amy Morayo , Adedokun Rahamon , Olaifa Abayomi , Oyagbemi Ademola , Omobowale Temidayo 
Published: June 2021

IntroductionApart from being a widely used antiprotozoal drug in many parts of Africa, Diminazene aceturate (DIZE), has been shown to have beneficial effects in experimental murine models of hypertension, pulmonary hypertension, myocardial infarction, stroke, atherosclerosis, type 1 diabetes, and eye disease. In this study, we investigated the effect of diminazene aceturate treatment after a single intramuscular administration on some cardiovascular parameters and antioxidant status in apparently healthy Nigerian horses.Materials and methodsTen male horses were divided into two groups comprising 5 horses each. Group A was the control group with no drug administered. Group B was treated with DIZE at 3.5 mg/kg, single dose. Baseline data were collected before the commencement of the experiment and thereafter, post‐administration at 0hrs, 24hrs, 48hrs and 96hrs. Base apex electrocardiogram was recorded using a computer ECG machine while oscillometric blood pressure measurement was recorded using a veterinary blood pressure monitor. Markers of oxidative stress were determined in the serumResultSingle intramuscular treatment caused a significant (p<0.05) increase in the systolic, diastolic and mean arterial blood pressure values when compared with the controls. From the electrocardiogram, sinus rhythm was recorded in both groups however, significant (p<0.05) increase in heart rate, p‐wave duration, QRS complex duration and QTc were observed in the treated group when compared with the control. Oxidative stress markers (malondialdehyde and hydrogen peroxide) significantly (p<0.05) increased while antioxidant enzymes (catalase, glutathione peroxidase and glutathione) were decreased when compared to the control.ConclusionThis study indicates that the use of DIZE in horses should be with great caution because of the associated cardiovascular physiological alterations, reduction in activities of antioxidant enzymes and increase in markers of oxidative stress.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Angiotensin converting enzyme inhibitors or angiotensin receptors blockers equally enhances skeletal structure via different metabolic influence
Authors: Abuohashish Hatem Mustafa 
Published: June 2021

The impact of renin‐angiotensin system (RAS) on bone remodeling and metabolism has gained more interest in recent years, where several RAS metabolites are deemed as potential targets for skeletal diseases. This study compares the effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin‐II (AngII) type‐1 receptor (AT1R) blockers on bone structure and remodeling and investigates the involvement of neutral endopeptidase enzyme (NEP) and angiotensin 1‐9 (Ang1‐9) in ovariectomized (OVX) rats. OVX animals received either captopril or losartan for 6 weeks. Both antihypertensive agents equally attenuated the elevated levels of bone metabolic bio‐markers and restored Ca2+ and phosphorous renal elimination and bone deposition. The altered bone cortical and trabecular morphometry in OVX rats was similarly ameliorated. In femurs heads, the expressions of NEP and Ang1‐9 were enhanced by captopril, while remained unchanged in losartan groups. In addition, both drugs down‐regulated the osteoclastogenesis inducing factor, receptor activator NF‐κB ligand (RANKL), while enhanced osteoprotegerin. Although, both antihypertensive agents had different influence on local skeletal RAS metabolism, losartan and captopril equally restored bone micro‐structure in estrogen deficient animals.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.