bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tangeretin Protects against Ethanol‐Induced Injury in Gastric Mucosa of Rats via its Antioxidants and Anti‐inflammatory Activity
Authors: Arafa El‐Shaimaa A. , Islam Mohammad Waseemul 
Published: June 2021

Tangeretin (TG), a polymethoxy citrus flavone, has attracted attention due to its significant antioxidant and anti‐inflammatory activities. It showed valuable pharmacological actions and protected against cancer, diabetic‐, liver‐ and renal‐induced injuries. However, its antiulcer activity has not been investigated.This study aimed to explore the possible protective effects of TG against ethanol‐induced gastric injury in rats. Adult male Wistar rats were used and divided into five groups: Control, TG, EtOH, EtOH+TG and EtOH+ Pantoprazole (PAN). Gastric injury was induced by a single dose of Absolute ethanol (5ml/Kg, p.0).Alcohol administration leads to significant macroscopic, histologic and biochemical gastric injuries. Treatment with TG (100mg/kg p.o.) protected against EtOH‐induced gastric injuries as demonstrated by the decrease in the ulcer and bleeding scores. Tangeretin boosted the antioxidants properties of the gastric mucosa via the inhibition of Malondialdehydes (MDA) and nitric oxides (NO) while improving glutathione (GSH), superoxide dismutase (SOD) and the nuclear factor erythroid 2–related factor 2 (Nrf2). Tangeretin curbed gastric inflammation by decreasing myeloperoxidase (MPO) and tumor necrosis factor‐α (TNF‐α) while increasing the anti‐inflammatory interleukin‐10 (IL‐10). In addition, TG caused the upregulation of the gastric cytoprotective prostaglandin E2 (PGE2). These results were comparable to those produced by PAN; the proton pump inhibitor.These findings reported for the first time the gastroprotective actions of TG in EtOH‐induced gastric injury which were mediated via suppression of inflammation and oxidative stress in addition to enhancing the antioxidant and the cytoprotective defenses.Support or Funding InformationThis work has been financially supported by the research grant# 2017‐A‐PH‐03 from the Deanship of Graduate Studies and Research, Ajman University.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Beneficial effects of aqueous extracts of Mikania glomerata Sprengel and Mikania laevigata Schultz Bip ex Baker on the inflammatory response in rats with acute pancreatitis
Authors: de Souza Pereira Della Pasqua Camila , Antunes Edson , Sawaya Alexandra Christine Helena Frankland , Campos Rafael , Landucci Ellen Cristina Teizem 
Published: June 2021

ObjectivesAccording to previous studies, aqueous extracts of Mikania glomerata (MG) and Mikania laevigata (ML) possess considerable anti‐inflammatory activity. Altogether, these findings suggest that these species has a potential effect in the treatment of inflammatory conditions, particularly those involving the gastrointestinal tract. In view of this, it is believed that these species may present important effects in the treatment of acute pancreatitis. Since there is no specific pharmacological therapy for acute pancreatitis, the elucidation of this parameter is the main objective of this study, in an attempt to prove the therapeutic efficacy of these plants under this condition.Material and MethodsThe extracts were characterized by Ultra High Efficiency Liquid Chromatography coupled to Mass Spectrometry (UHPLC‐MS). The animals were treated per oral route (p.o.), through the gavage technique, in the final volume of 500 μL, for 7 consecutive days and then submitted to induction of acute pancreatitis (AP). Male Wistar rats were submitted to injection of sodium tauracholate (30 mg/kg) into the common bile duct. After 4 hours the animals were sacrificed, when blood, pancreas and left lung were collected for analysis of pancreatic edema, pancreatic and pulmonary neutrophil infiltrate (MPO), elevation of serum amylase, TNF‐α in serum and interleukins.Results and DiscussionInduction of AP by sodium tauracholate significantly increased all the parameters evaluated when compared with the respective sham group. The pretreatment with MG (400 mg/kg) significantly reduced pancreatic oedema, pancreas and lung MPO activity. The same profile of reduction was observed in the pretreatment with coumarin (75 mg/kg). The pretreatment with ML showed a significant reduction for all doses tested in the pancreatic oedema and lung MPO activity. For pancreas MPO activity, the doses of 200 and 400 mg/kg showed significant reduction of this parameter.ConclusionOur results showed that aqueous extracts of M. glomerata and M. laevigata decreases inflammation acute pancreatitis, making it of interest in future approaches to treat this condition. However, additional studies are being made by our group to establish the effectiveness of this mechanism.Support or Funding InformationCamila S. P. Della Pasqua is a fellowship of National Council for Scientific and Technological Development (CNPQ).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Western diet increases HMGB1 levels and activates cardiac and hepatic Toll‐like receptor 4 (TLR4) signaling in male mice
Authors: Soultan Kimberly Mae , Carrillo‐Sepulveda Maria Alicia 
Published: June 2021

BackgroundOverconsumption of a Western diet (WD), characterized by a high amount of fats and carbohydrates, is a major contributor to the epidemic of non‐alcoholic liver and cardiovascular disease in the United States. Our laboratory has recently demonstrated that WD causes endothelial dysfunction via vascular TLR4 signaling activation, a key component of innate immunity linked to inflammation. Based on these findings, we hypothesized that WD triggers inflammatory responses in the livers and hearts of male mice via activation of TLR4 signaling. We also investigated whether WD elevates high‐mobility group box 1 protein (HMGB1) levels, a pro‐inflammatory factor known to be an endogenous ligand for TLR4.MethodsAdult male C57BL/J mice were randomized in two experimental groups: Control Group received a regular chow diet and WD group received WD (40% fat, 43% carbohydrates, and 17% protein) for 28 weeks. Prior to terminal experiments, body weights were measured weekly. After euthanasia with isoflurane (via nasal 5% in 100% O2), livers, hearts, and adipose tissue were removed and processed for further molecular assays. Blood samples were also obtained for biochemical analysis.ResultsAs expected, WD group exhibited increased body weight (31.1 ± 3.2 vs. 25.2 ± 1.4g, p<0.01), adipocyte size (7724.2 ± 1745.8 vs. 2727.3 ± 927.1 μm2, p<0.05) and elevated serum free fatty acids (0.20 ± 0.02 vs. 0.14 ± 0.024 mM, p<0.05) compared to controls. Next, to test the hypothesis that WD activates TLR4 signaling in hepatic and cardiac tissue, Western blot analysis was performed. Hepatic expression of TLR4 (2.8 fold increase vs. controls, p<0.001) and its downstream protein TNF receptor‐associated factor 6 (TRAF6) (1.8 fold increase vs. controls, p<0.01) were markedly elevated in the WD group. Similarly, cardiac expression of TLR4 (2.2 fold increase vs. controls, p<0.01) and TRAF6 (2.8 fold increase vs. controls, p<0.001) were increased in the WD group. Strikingly, we found that serum HMGB1 expression was significantly increased in WD group in comparison to the controls (70% elevation vs control, p<0.05).ConclusionOur results suggest that upregulation of HMGB1 may contribute to TLR4/TRAF6 signaling activation in hepatic and cardiac tissue of western diet fed mice. To expand this investigation, we will utilize pharmacological and molecular approaches to target HMGB1 and confirm its role in WD‐induced inflammation.Support or Funding InformationIn‐house Grant NYITThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dexamethasone regulates Hox and paraHox gene expression in mouse liver
Authors: Ji Yue , Cheng Xingguo 
Published: June 2021

The homeobox (Hox) genes encode homeodomain proteins, which control the development of body forms of many organisms including plants, Drosophila, mouse, and human. Dexamethasone (DEX), a synthetic glucocorticoid with potent anti‐inflammatory effects, can activate pregnane X receptor (PXR) and glucocorticoid receptor (GR) nuclear receptors in a dose‐dependent manner. At low doses such as 2 mg/kg, DEX activates only GR in mouse liver. However, at higher doses such as 50 mg/kg, DEX activates both GR and PXR nuclear receptors. Few studies have reported that DEX can regulate the expression of Hox genes. The purpose of this study was to determine the regulation of Hox (including Hox a‐d subfamily members) and paraHox genes by DEX in mouse liver, as well as the underlying mechanism. Adult male C57BL/6 mice were treated with DEX (2 and 50 mg/kg) once daily for 7 days (n=4–6/treatment). Our results showed that: 1) 2 mg/kg of DEX did not alter mRNA expression of any Hox a–c subfamily members. 2) 50 mg/kg of DEX induced mRNA expression of many Hox a (including Hox a2, a3, a9, a10, a11, and a13), Hox b (including Hox b2, b4, b5, b6, b7, and b9), and Hox c (including Hox c4, c5, c9, c10, c11, and c13) subfamily genes. 3) 2 mg/kg of DEX induced mRNA expression of Hox d9, d11, and d12; whereas 50 mg/kg of DEX induced mRNA expression of Hox d1, d3, d4, d8, d9, d10, d11, and d12. And 4) DEX at the dose of 50 mg/kg but not 2 mg/kg, induced mRNA expression of several other Hox and paraHox genes, including Hex, Pbx1, Gsh1, and Cdx. In conclusion, DEX at the dose of 50 mg/kg but not 2 mg/kg up‐regulated mRNA expression of many Hox and paraHox genes in mouse liver, indicating that signaling of PXR but not GR is involved in Hox and paraHox gene expression.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structure‐Based Assessment of the Toxicity and Cytoprotective Effects of a Series of Small Molecule Polyphenolic Compounds
Authors: Lotomau Storm , Yavuz Ege , True Heather , Stamper Brendan 
Published: June 2021

ObjectivePolyphenols are widely known to possess antioxidant and anti‐inflammatory properties, but are also capable of eliciting toxicity at higher doses. This goal of this project was to investigate whether a structure‐toxicity relationship exists among five polyphenolic compounds: trans‐cinnamic acid (tCA), p‐coumaric acid (COU), caffeic acid (CAF), resveratrol (RES), and phloretin (PHL). Each compound is relatively similar in structure, but varies in the number of phenolic groups it contains (tCA=0, COU=1, CAF=2, RES=3, PHL=4).MethodsPolyphenol toxicity was measured by determining the median lethal dose (LC50) and toxicant threshold concentration (LC1) for each compound using an in vitro mouse liver model (TAMH; transforming growth factor‐α transgenic mouse hepatocytes). TAMH cells were cultured and exposed to varying concentrations of each compound for 24‐hours followed by a test for cell viability using resazurin dye. Subsequent hepatoprotective studies based on LC1 values were then conducted by incubating TAMH cells with each polyphenol for 24 h prior to a hepatotoxic dose of diquat (18μM). Changes in cell viability were again measured using the resazurin‐based assay. Data analysis was performed using SPSS to calculate the LC50 and LC1 values for each compound. Significance was determined using one‐way analysis of variance (ANOVA) and post‐hoc Least Significant Difference tests with a fold cut‐off of p < 0.05.ResultstCA and COU were relatively non‐toxic (LC50 > 5mM) compared to the compounds with multiple phenolic groups. In fact, addition of phenolic groups directly correlated with a decrease in the LC50 value indicating that as the number of phenolic groups increased so did the toxicity for this series of compounds. For the hepatoprotection studies, significant increases in cell viability were observed across only some of the polyphenolic compounds; however, this protection did not correlate with phenolic group number.ConclusionsWhile greater toxicity was associated with an increase in the number of phenolic groups based on the LC50 determinations, no common trend was observed relating phenolic group number and hepatoprotective ability using an LC1‐based dosing regimen. Perhaps this suggests that subtle differences in the carbon skeleton among the polyphenols tested influences protective ability. Future work is currently underway to investigate the mechanistic features differentiating the degree of cytoprotection between the polyphenolic compounds.Support or Funding InformationSource of Research Support: This work was supported by the Pacific University Research Incentive Grant Program and an ASPET Summer Undergraduate Research Fellow (SURF) Individual Award.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 trichloroethene‐mediated autophagy, inflammasome activation, and hepatic immune dysregulation by N‐acetylcysteine
Authors: Wang Hui , Wang Gangduo , Liang Yuejin , Du Xiaotang , Sun Jiaren , Boor Paul J. , Khan M. Firoze 
Published: June 2021

Trichloroethene (TCE) exposure can cause induction of autoimmune diseases (i.e., autoimmune hepatitis and systemic lupus erythematosus) potentially through increased oxidative stress (OS). Activation of autophagy has emerged as a pivotal pathogenic factor in various autoimmune diseases. However, role of OS in the regulation of autophagy leading to autoimmune diseases is largely unknown. Here, we tested the hypothesis that OS‐induced activation of autophagy and inflammasome contribute to induction and pathogenesis of TCE‐mediated autoimmune diseases. Female MRL +/+ mice were treated with TCE along with or without antioxidant N‐acetylcysteine (NAC) for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day via drinking water). TCE‐treated mice had elevated anti‐nuclear antibodies (ANA) and anti‐4‐hydroxynonenal (HNE)‐specific circulating immune complexes, suggesting the association of TCE‐induced OS with autoimmune response. Moreover, TCE exposure led to hepatic autophagy activation as evident from increased beclin‐1 and autophagic light chain 3 conversation (LC3‐II/LC3‐I). The TCE‐mediated autophagy activation was associated with activation of hepatic inflammasome (NLRP3 and caspase‐1) and up‐regulated pro‐inflammatory cytokine IL‐1β. TCE exposure led to hepatic morphological changes, including sinusoid dilation, increased sinusoidal cellularity and proliferating cell nuclear antigen (PCNA) intensity. In addition, dysregulation of hepatic immune response was also observed as evident from markedly increased hepatic lymphocyte infiltration and imbalance between Tregs (decreased) and Th17 cells (increased). Remarkably, TCE‐mediated increased autoantibody formation, hepatic activation of autophagy and inflammasome, and immune dysregulation were effectively attenuated by NAC. Taken together, these results suggest that TCE mediated the hepatic immune dysregulation via OS and activating autophagy and inflammasome. Amelioration of these responses by NAC further supports the role of OS in TCE‐mediated autoimmunity. These novel findings could help in designing therapeutic strategies for such autoimmune diseases.Support or Funding InformationSupported by NIH R01 grants ES026887 and ES016302.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impacts on Hepatic Ontogenic Expression of Drug‐metabolizing Enzymes by High‐fat Diet‐induced Obesity in Mice
Authors: Wang Pei , Shao Xueyan , Bao Yifan , Chen Liming , Zhang Lirong , Zhong Xiaobo 
Published: June 2021

The prevalence of obesity‐associated conditions increases up to 30% of general populations globally. A few studies have shown that obesity may lead to altered drug metabolism. Although changed expression of drug‐metabolizing enzymes (DMEs) is reported, the impacts on DMEs due to different obese levels (overweight, obese, and morbidly obese) have not been elucidated. Especially, limited information is available on how obesity alters the expression of DMEs in younger ages. The aim of this study is to investigate impacts of high‐fat diet‐induced obesity (DIO) on the hepatic expression of DMEs in adult and the ontogenic expression in offspring with a focus on cytochrome P450s (CYPs) in a mouse model. The expression of CYPs, as well as constitutive androstane receptor (CAR), pregnane X‐receptor (PXR), hepatocyte nuclear factor (HNF4α), and peroxisome proliferator‐activated receptor α (PPARα) was examined. Adult mice consumed 60 kcal% fat diet (HFD) for 8 or 18 weeks showed a more rapid increase of body weight than 10 kcal% fat diet (LFD) control group. The body weight gain of males was >1.5 fold greater than females in HFD groups. Consistent with the weight gain, fat accumulation was found in the livers of HFD groups. Elevated expression of most selected DMEs and transcription factors was observed in HFD groups, expect for CYP3A16 in 8‐week HFD groups, and CYP1A2 and HNF4α in 18‐week HFD groups. Day 60 offspring derived from HFD‐fed adults showed heavier body weights compared with offspring from LFD‐fed adults. Altered ontogenic expression of CYP1A1, 1A2, 2E1, and UGT1A1 was also observed in HFD offspring. Notably, the changed ontogenic patterns were accompanied by the increased expression of DMEs after day 20 in HFD offspring related to LFD groups. Moreover, similar effects on CAR, PXR, HNF4α, and PPARα were found in HFD offspring, indicating that altered expression pattern of DMEs may due to changed expression of transcription factors. Taken together, our study suggested that obese level of DIO influenced the expression of DMEs in adults and offspring and transcription factors might play roles in the altered expression of DMEs.Support or Funding InformationThis work was supported by grant of NIH R01GM118367 and China Scholarship Council (201707040007).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Development of an inducible CRISPR/Cas9 system for temporally‐modulated gene editing
Authors: Olivas Micah , Fox Doug , Alvarez James 
Published: June 2021

Despite its prolific track record of research into primary tumor dynamics, the field of cancer biology has yet to develop a reliable methodology for interrogating the genetic profiles of recurrent tumors. CRISPR/Cas9 gene editing has proven to be foundational for recent advancements in oncogenetic screening, due in part to its high degree of specificity in achieving on‐target gene knockout while minimizing off‐target effects. The primary limitation to its application in screening pro‐recurrence factors in cancer, however, is the constitutive nature of canonical Cas9 activity, which may not be remotely regulated after the point of Cas9 translation. To address this problem, we cultivated and transduced populations of a resected invasive mammary adenocarcinoma cell type with a selection of four recombinant Cas9 transgenes and characterized the relative inducibility of each system. These Cas9's are fused to peptides whose tertiary structure renders the endonuclease inactive, restoring catalytic activity only in the presence of a fusion‐specific ligand. Populations of EGFP‐expressing adenocarcinoma cells were transduced with a modified estrogen receptor‐Cas9 fusion (ERT2‐Cas9) and assayed for target knockout efficiency upon addition of small guide GFP (sgGFP) and a Cas9‐enabling estrogen analog. After three days exposure to the analogue, flow cytometry revealed GFP expression to be markedly reduced in cells expressing ERT2‐Cas9 and minimal change in those not exposed. Once the timing and treatment of this model are refined, ERT2‐Cas9‐expressing adenocarcinoma cells will be orthotopically‐injected into mice for an in vivo screening assay. By equipping neoplastic cells with the inducible‐Cas9 machinery before the point of tumor outgrowth, it becomes possible to systematically screen pro‐survival factors at late time points in cancer progression without drastically disturbing the microenvironment of the tumor.Support or Funding InformationThis work was supported by ah ASPET summer research award in partnership with SURPH at Duke University.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 Cystathionine‐Gamma‐Lyase/Hydrogen Sulfide System Modulation on Vascular Dysfunction Induced by Insulin Resistance in Male Wistar Rat Thoracic Aorta
Authors: Silva‐Velasco Diana Laura , Hong Enrique , Beltran‐Ornelas Jesus Hernan , Sánchez‐López Araceli , Gomez Carolina Belen , de la Cruz Saul Huerta , Centurion David 
Published: June 2021

Hydrogen sulfide (H2S) is a novel gasotransmitter synthetized from L‐Cysteine by three enzymatic pathways. In blood vessels, cystathionine‐gamma‐lyase (CSE) is mainly expressed and regulates vascular function. This enzyme may be affected by insulin resistance. Insulin resistance leads to vascular dysfunction and is the major mechanism underlying type 2 Diabetes Mellitus. The aim of this study was to determine the effect of chronic administration of sodium hydrosulfide (NaHS; inorganic H2S donor), L‐Cysteine (L‐Cys; substrate of H2S producing enzymes) and DL‐Propargylglycine (DL‐PAG; CSE inhibitor) on the vascular dysfunction induced by insulin resistance in male Wistar rat thoracic aorta. For that purpose, animals were divided into two main sets that received for 20 weeks: (1) tap water (control group; n=6); and (2) 15% p/v fructose in drinking water (insulin resistance group; n=30). Then, the insulin resistance group were divided into 5 subgroups (n=6 each) which received daily i.p. injections during 4 weeks of: (1) nothing (without pharmacological administration); (2) vehicle (phosphate buffer saline; PBS, 1 ml/kg); (3) NaHS (5.6 mg/kg); (4) L‐Cys (300 mg/kg); and (5) DL‐PAG (10 mg/kg). After 20 weeks, metabolic (oral glucose tolerance test, plasma insulin levels, and Matsuda‐index) and hemodynamics variables by tail‐cuff method as well as vascular function by in vitro experiments were determined. Fructose‐induced insulin resistance leads to: (1) hypertension (without affecting heart rate); (2) hyperinsulinemia; (3) a decrease in Matsuda‐index; and (4) a decrease in carbachol‐induced vasorelaxant responses with no effect on the contractile responses to noradrenaline. Interestingly, after 4 weeks of treatment, NaHS decreased blood pressure and restored vasorelaxant responses to carbachol with no effect on metabolic variables while L‐Cys improved the contractile and vasorelaxant responses to noradrenaline and carbachol, respectively, when compared to vehicle (PBS). On the other hand, DL‐PAG induced a slightly increase in systolic and median blood pressure with no effect on the contractile response to noradrenaline or relaxant responses to carbachol as well as metabolic variables compared to vehicle. Taken together, these results suggest that chronic treatment with NaHS and L‐Cys improved vascular dysfunction and hypertension induced by insulin resistance and may have a potential therapeutic application.Support or Funding InformationThe authors acknowledge to Conacyt (Grant No. 252702) for its financial support.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.