bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palmatine Identified from Malaysian Local Plant Possess In vitro and In vivo Antidiabetic and Antioxidant Effect on High‐Fat Diet‐Induced Diabetic Rat Model
Authors: Okechukwu Patrick Nwabueze , Ekeuku Sophia Ogechi , Sharma Mridula , Fromming Gabriele Ruth Anisah 
Published: June 2021

BackgroundCoscinium fenestratum (CF) (Gaertn.) Colebr is from the family Menispermaceae, is a woody plant found in Southeast Asia including Malaysia. Traditionally CF has been used for the treatment of many diseases including diabetes Mellitus. Our previous research identified Palmatine a protoberberine alkaloid to be the active bioactive compound present in CF.ObjectiveThe aim of this study was to investigate in vitro and in vivo anti‐diabetic, antioxidant Effect on High Fat Diet Induced Diabetic Rat Module.MethodThe ability of Palmatine to inhibit reactive oxygen specie (ROS) such as Lipid peroxidation, DPPH, Nitric oxide, Hydroxyl, free radical scavenging activity was evaluated. The in vitro antidiabetic activity of Palmatine was evaluated using alpha glycosidase, alpha amylase and Dipeptidyl peptidase IV enzyme. Sprague dawley rats weighing 180–200g was fed with high fat diet (HFD) for 60 days to induce diabetes. Rats with plasma glucose level of 11mmol/L or 200mg/dL and above after 60 days HFD feeding, were orally administered with Palmatine (2mg/kg) for 90 days. The plasma glucose level and body weight of the rats were measured weekly. After treatment, the rat blood was withdrawn via cardiac puncture for hematological studies. Liver and pancreas was harvested for antioxidant, histology, biochemical and lipid profile analysis.ResultPalmatine was able to inhibit free radicals generated by Nitric oxide, DPPH, Hydroxyl, and alpha glucosidase, and alpha amylase activities. Palmatine was able to reduce plasma glucose level, activate antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase and inhibit lipid peroxidation in HFD induced diabetic rats. Biochemical and hematological analysis showed a reduction of diabetic markers in rats such HbA1c, urea, alkaline phosphatase, aspartate transaminase, alanine aminotransferase, LDL‐cholesterol, Triglycerides, but increase HDL level.ConclusionPalmatine possess antidiabetic and antioxidant in HFD induced diabetic rat model and able to offer protection to kidney, liver and cardiovascular organs by reducing the disease markers (Diabetes Complication Prevention).Support or Funding InformationCentre of Excellence for Research, Value, Innovation and Entrepreneurship Research Grant Scheme UCSI University (UCSI‐CERVIE‐RGS Proj‐in‐FAS 039)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of Prenatal Dexamethasone on Circulating Cytokines and Chemokines in Neonatal and Adult Rats
Authors: Madhavpeddi Lakshmi , Hammond Bradley , Hale Taben , Handa Robert 
Published: June 2021

Dexamethasone (DEX) is a synthetic glucocorticoid administered to mothers at risk for pre‐term labor. We and others have shown that prenatal DEX produces long‐term changes in the hypothalamic pituitary adrenal axis and cardiovascular function in adult offspring. However, there is limited information regarding the longitudinal impact of in utero DEX exposure on the immune system. In the present study, we determined the plasma levels of 20 cytokines and chemokines in male and female neonatal and adult rats that had been exposed to DEX in utero. Pregnant dams were administered DEX (0.4mg/kg or 0.1mg/kg per day, s.c.) or vehicle on gestation days 18–21. A subset of rats was sacrificed at post‐natal day 0 (PND0) and remaining rats were weaned at post‐natal day 21 and sacrificed at 2.5 – 3 months of age for measurement of plasma cytokine and chemokine levels. At PND0, plasma Il‐1β was reduced only in DEX‐exposed males, while the lymphocyte chemoattractant IP‐10 was only increased in DEX‐exposed females. In contrast, the levels of monocyte chemoattractant protein‐1 (MCP‐1) at PND0 were elevated in both males and females that were exposed to DEX in utero. Although increased MCP‐1 levels continued to be elevated in adult females that were prenatally exposed to DEX, this chemokine was significantly reduced in DEX‐exposed adult males. Moreover, DEX‐exposed male, but not female adult offspring displayed reduced circulating levels of Il‐2, Il‐17α, Il‐18, and TNFα. Taken together, prenatal DEX results in persistent and sex‐specific changes in circulating levels of inflammatory mediators. Further studies will determine the long‐term consequence of this age‐ and sex‐related changes of DEX on immune function.Support or Funding InformationABRC ADHS14‐082990This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
ANTIMICROBIAL ASSAY OF CARESOO ELECTROLYZED WATER: Part II. Comparative Study on the Antimicrobial Activity of Sulfamylon solution, Dakin's solution, commercially available hypochlorous acid and the electrolyzed water from Caresoo hypochlorous acid water generator
Authors: Atanacio Ronald , Malbas Fedelino , Mondoy Melisa , Cavo Betty , Galit Salvacion Rosario , Alvarado‐Delacruz Kristine , Sarte Roan May , Atanacio Enriquito 
Published: June 2021

In the initial study conducted, the electrolyzed water from Caresoo hypochlorous acid water generator affirmed to have bioactivity against pathogenic microorganisms. Part II of this study is to compare the bioactivity of sulfamylon solution, Dakin's solution, and commercially available hypochlorous acid against electrolyzed water from Caresoo hypochlorous acid water generator.Electrolyzed water was prepared and tested against Staphylococcus aureus, Methicillin Resistant Staphylococcus aureus (MRSA), Methicillin Resistant Staphylococcus epidermidis, (MRSE) Pseudomonas aeruginosa, Streptococcus pyogenes, Proteus mirabilis and Candida albicans. The antimicrobial activity of the electrolyzed water was compared with the bioactivity of the full strength Dakin's solution, 100% sulfamylon solution and commercially available hypochlorous acid in 3 replicates using Mac Farland.The electrolyzed water exhibited bioactivity in all test organisms less than 15 seconds after inoculation. The same results were obtained in commercially available HOCl (V). Full strength Dakin's solution and 100% sulfamylon solution showed complete antimicrobial activity after 30 minutes of inoculation.The antimicrobial activity of the electrolyzed water from Caresoo® Hypochlorous Acid Water Generator affirms its potential as a pharmacological agent in treating and controlling infection as compared to full strength Dakin's solution and sulfamylon solution.Support or Funding InformationResearchers funded this project.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Histone Deacetylase Inhibitors Attenuate Hepatic Fibrosis through Suppression of Group 2 Innate Lymphoid Cells and Type 2 Inflammation
Authors: Iyer Abishek , Loh Zhixuan , Fitzsimmons Rebecca L , Reid Robert C , Ramnath Divya , Clouston Andrew , Irvine Katharine M , Powell Elizabeth E , Schroder Kate , Stow Jennifer L , Sweet Matthew J , Fairlie David P 
Published: June 2021

Deposition of collagen and matrix proteins is essential for tissue repair and remodelling. Chronic liver diseases typically show excessive matrix protein deposition or crosslinking that leads to scar tissue, obstructs blood flow and disrupts liver functions, all characteristics of advanced liver damage in cirrhosis. There are no effective anti‐fibrotic therapies. Immunomodulatory mechanisms that contribute to fibrogenesis in chronic liver disease are not fully elucidated. Here we examine thioacetamide‐induced liver injury in mice, which develop progressive hepatic inflammation and fibrosis similar to clinical features of chronic human liver disease. We find that inhibitors of class I, but not class II, histone deacetylase (HDAC) enzymes suppress hepatic inflammation and fibrosis in this model. Inhibitors of class I HDACs attenuate accumulation and activation of group 2 innate lymphoid cells (ILC2), specifically interleukin (IL)‐33 (but not IL‐25) dependent CD45+/Lin−/Thy‐1+/ST2+/KLRG1int ILC2 cells, associated with type 2 inflammation that drives hepatic stellate cells to secrete excessive matrix proteins. Some HDAC inhibitors that are registered anti‐cancer drugs might be repurposed for treating chronic liver fibrosis.Support or Funding InformationZL acknowledges salary support from the Centre for Inflammation and Disease Research, University of Queensland. The National Health and Medical Research Council of Australia is acknowledged for a Career Development Fellowship to KS (1141131), a Senior Research Fellowship to MJS (1107914) and a Senior Principal Research Fellowship to DPF (1117017).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Silencing Fatty Acid Binding Protein‐4 Through Percutaneous Retro‐orbital Injections Attenuates Inflammation in ApoE−/− Mice Liver
Authors: Prathipati Priyanka , Rodriguez‐Aguayo Cristian , Walton Brian , Sood Anil , Lopez Gabriel Berestein 
Published: June 2021

BackgroundFatty acid binding protein‐4 (FABP4) is a lipid chaperon is an important regulator of atherosclerosis and inflammation. We hypothesize that silencing FABP4 could be a novel therapeutic treatment for atherosclerosis, in turn liver inflammation. Hence a liposomal small interfering RNA (siRNA) delivery system to silence FABP4 was developed.MethodsMale ApoE mice (N=16) were fed high fat diet from 6 weeks of age until 12–16 weeks. At 11 weeks of age, the mice were injected with 0.1ml (500µg/ml) of FABP4/control siRNA liposomes tagged with fluorescent Qdot (QD) 625. The injections were administered through percutaneous retro‐orbital route twice a week for four consecutive weeks. Starting in the 12th week, two mice from each group were sacrificed every week. Aortas, serum and livers were collected at the time of sacrifice, parts of these organs were stored in formalin and processed for paraffin sections and part of them were flash frozen for protein analysis. FABP4 in aortas and livers along with the pro‐inflammatory markers (IL‐6) in livers were analyzed by western blot and immunohistochemistry. This investigates the effect of FABP4 siRNA liposomes on atherosclerosis and inflammation in liver.ResultsSilencing FABP4 in ApoE mice attenuates the inflammation in liver compared to the control siRNA treatment (Figure).ConclusionPercutaneous retro‐orbital injections of FABP4 siRNA liposomes for four consecutive weeks might help to attenuate liver inflammation in ApoE mice.Effect of FABP4 silencing on liver inflammationSilencing FABP4 attenuated the expression of pro‐inflammatory marker in the livers of ApoE−/− mice.Support or Funding InformationThis work was supported by Gillson Longenbaugh Foundation (9091‐001‐N‐1 & G2015)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Vitamin D Promotes Anti‐inflammatory Phenotype as Opposed to Proinflammatory State of Macrophages
Authors: Othman Tesneem , Jarjes Lelein , Hermes Erin L , Tauseef Mohammed , Siddiqui Rizwan , Faridi Hafeez M , Khan Mohammed , Newaz Mohammad , Wu Mei X , Shahid Mohd 
Published: June 2021

Vitamin D (Vit‐D) deficiency is linked to several metabolic diseases such as atherosclerosis and obesity. However, the underlying mechanism remains elusive. Immediate early response gene x‐1 (IEX‐1)—which is negatively regulated by Vit‐D—is recently shown to play a crucial role in the pathogenesis of obesity and atherosclerosis. Its paucity prevents anti‐to‐pro‐inflammatory shift in macrophage phenotype and thereby protecting against these diseases. We hypothesize that Vit‐D protects against the metabolic disease partly by inhibiting pro‐inflammatory macrophages via repressing IEX‐1. We cultured RAW 264.7 cells, a murine macrophage cell line in DMEM, and pretreated them with different doses of Vit‐D (0.1, 1, and 10 nM) for 8 hours. The cells were then differentiated into pro‐ or anti‐inflammatory macrophages by treatment with LPS (10 ng/ml) and IL‐4 (10 nM), respectively, for 24 hours in the absence/presence of Vit‐D. Total cellular RNA was extracted using Trizole and cDNA was synthesized. The mRNA levels of IEX‐1, pro‐, and anti‐inflammatory genes were determined using quantitative RT‐PCR. The protein levels of TNF‐α and IL‐10 were measured in culture supernatant using ELISA. LPS treatment increased mRNA levels of proinflammatory genes IL‐6 (60±6‐fold, p<0.001), TNF‐α (8±0.7‐fold, p<0.01), and iNOS (10±0.7‐fold, p<0.01) in RAW cells. Pretreatment with 10 nM Vit‐D but not 0.1 or 1 nM significantly inhibited LPS‐induced increases in expression levels of IL‐6 (24±2‐fold, p<0.01), TNF‐α (4±0.3‐fold, p<0.05), and iNOS (4.7±0.3‐fold, p<0.05 versus LPS alone). Vit‐D also suppressed LPS‐induced TNF‐α protein production by macrophages (18±0.8 versus 27±1.4 ng/ml, p<0.05). On the other hand, IL‐4 treatment induced expression levels of anti‐inflammatory genes Arg‐1 (93±18‐fold, p<0.01), MRC‐1 (2±0.1‐fold, p<0.05), and Clec10a (2.2±0.2‐fold, p<0.001), suggesting the formation of alternatively activated macrophages. Interestingly, pretreatment with Vit‐D dosedependently potentiated IL‐4‐induced increases in Arg‐1, MRC‐1, and Clec10a mRNA levels. Specifically, Vit‐D at 10 nM markedly increased expression levels of Arg‐1 (287±51‐fold, p<0.01), MRC‐1 (6±0.8‐fold, p<0.05), and Clec10a (6±0.8‐fold, p<0.001 versus IL‐4 alone) induced by IL‐4. Vit‐D also increased IL‐4‐induced IL‐10 protein production (510±41 versus 748±36 pg/ml, p<0.05). Concurrently, Vit‐D treatment dose‐dependently repressed IEX‐1 expression in RAW cells, confirming negative regulation of IEX‐1 by Vit‐D. These results suggest that Vit‐D promotes the anti‐inflammatory state of macrophages likely in part, by repressing IEX‐1 expression.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.
Expression Regulation of Hox Genes by Perfluorochemicals in Mouse Liver
Authors: ZHANG YUE , CHENG XINGGUO 
Published: June 2021

Homeobox (Hox) genes encode homeodomain proteins, which play important roles in the development and morphological diversification of plants and animals. Perfluorochemicals (PFCs), which are the persistent environmental pollutants and frequently detected in human blood, can interfere with animal development. PFCs produce numerous hepatic adverse effects, such as increased peroxisomes, hepatomegaly and altered lipid metabolism, primarily via activation of peroxisome proliferator‐activated receptors (PPARs) and/or constitutive androstane receptor (CAR). No study has reported that PFCs can regulate the expression of Hox genes. This study was designed to determine the expression regulation of Hox and paraHox genes by perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) in mouse liver. A single dose of 0.1 mmole/kg PFOA, PFNA and PFDA was intraperitoneally administered to adult male wild‐type, and age‐matched male PPARα‐null and male CAR‐null mice (n=6/treatment). Four days later, mouse livers were collected and processed. Messenger RNA expression of Hox genes (including Hox‐a to ‐d subfamily members) and paraHox genes (including Gsx, Pdx, and Cdx gene family members) were determined. Our results showed that PFOA, PFNA, and PFDA all induced mRNA expression of Hoxb7, c5, d10 and Zeb2 in wild‐type mouse liver, but not in PPARα‐null mouse liver. We further showed that PFNA induced mRNA expression of Hoxa5, b7, c5, c8, and d10 in livers of wild‐type and CAR‐null mice, but not in PPARα‐null mouse liver, indicating a PPARα‐dependent mechanism. Furthermore, knocking‐out of PPARα or CAR in mouse liver decreased constitutive mRNA expression of Hoxc5. Wy‐14643, a classical PPARα agonist, induced mRNA expression of Hoxc5, but not of Hoxa5, b7 or d10 in wild‐type mouse liver. 1,4‐bis‐[2‐(3,5,‐dichloropyridyloxy)] benzene (TCPOBOP), a classical CAR agonist, also induced mRNA expression of Hoxc5, but not of Hoxa5, b7 or d10 in wild‐type mouse liver. Messenger RNA expression of studied paraHox genes were not apparently altered by PFCs in mouse liver. In conclusion, perfluorochemicals induced mRNA expression of certain Hox genes such as Hoxc5, maybe via activation of PPARα and/or CAR.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization of the Expression and Function of Rheostat Locations within the Na+/Taurocholate Cotransporting Polypeptide
Authors: Ruggiero Melissa , Swint‐Kruse Liskin , Hagenbuch Bruno 
Published: June 2021

BackgroundThe Na+/taurocholate cotransporting polypeptide (NTCP) is a sodium dependent bile acid transporter expressed at the basolateral membrane of human hepatocytes. NTCP is important for the enterohepatic circulation of bile acids, such as taurocholate. It also transports the steroid hormone estrone‐3‐sulfate and the cholesterol lowering drug rosuvastatin. We have previously identified rheostat positions in NTCP. These are positions at which replacement of an amino acid to all other 19 amino acids results in a gradual change in function, whereas all‐or‐nothing changes are known as toggle locations. One of these rheostat positions is the naturally occurring polymorphic position S267.AimThe purpose of the current study is to characterize the effects of amino acid replacements at S267 with respect to expression and function.MethodsNTCP mutants were generated using site‐directed mutagenesis, and the mutated proteins were transiently expressed in HEK293 cells. Surface biotinylation assays were performed to determine plasma membrane expression levels. Functional characterization was achieved using radiolabeled model substrates: [3H]‐taurocholate, [3H]‐estrone‐3‐sulfate, and [3H]‐rosuvastatin. After determining initial linear rate conditions, concentration dependent uptake was measured and kinetic parameters were calculated using the Michaelis‐Menten equation.ResultsSurface biotinylation experiments suggest that many mutants are expressed at a similar level as wild‐type NTCP. However, S267Q which showed slightly decreased taurocholate uptake, normal estrone‐3‐sulfate transport, and significantly decreased transport of rosuvastatin in our initial experiments, was expressed in extremely low amounts at the protein and membrane level. Thus, after normalization, S267Q exhibited a two‐ to ten‐fold increase in function. Another mutant, S267W, showed decreased taurocholate uptake but stimulated transport of estrone‐3‐sulfate and rosuvastatin. Comparison of this mutant's kinetics with that of wild‐type NTCP suggests that the affinity for taurocholate is decreased while the affinity for rosuvastatin is increased, explaining the observed initial altered transport.ConclusionsOur results suggest that the functional outcome of mutations at S267 is mainly due to changes in substrate affinity rather than protein expression. Future experiments will assess whether this is also true for other rheostat positions.Support or Funding InformationP20 GM103549, P30 GM118247, GM077336, and W. M. Keck FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of Cyclic Nucleotide Efflux by Placental MRP Transporters Enhances Trophoblast Syncytialization
Authors: Gorczyca Ludwik , Aleksunes Lauren 
Published: June 2021

In the placenta, multinucleated syncytiotrophoblasts arise from the fusion of cytotrophoblasts, a process regulated by cyclic nucleotide (cAMP and cGMP) signaling. Syncytiotrophoblasts secrete hormones and express efflux transporters, including the multidrug resistance‐associated proteins (MRP) 1 and 5. Understanding the interplay of cyclic nucleotides, efflux transporters, and syncytialization is important because aberrant cytotrophoblast functioning contributes to the pathogenesis of placental diseases and toxicities. In the present study, we sought to determine whether MRP transporters regulate the syncytialization of human placental cells. BeWo b30 trophoblasts were treated with vehicle, MK‐571 (25 μM), 8‐Bromo‐cAMP (100 μM), forskolin (25 μM), IBMX (200 μM), or their combination for up to 24 hr. Markers of trophoblast cell fusion (glial cells missing homolog 1, GCM1; syncytin 2) and hormone secretion (human chorionic gonadotropin, hCGa and hCGb) were quantified by qPCR. Treatment of BeWo cells with MK‐571, a pharmacological inhibitor of MRPs, increased intracellular concentrations of cAMP and cGMP by 15‐ and 19‐fold, respectively. Moreover, MK‐571 treatment up‐regulated cell fusion and hormone secretion markers (GCM1, hCGa, hCGb, syncytin 2) by 20–200% under basal conditions. Similarly, MRP inhibition with MK‐571 further enhanced syncytialization and hormone markers following stimulation with the permeable cAMP analog 8‐Bromo‐cAMP (2‐ to 6‐fold), activation of cAMP synthesis with forskolin (20–160%), or inhibition of cAMP/cGMP breakdown by IBMX (50–130%). In addition, shRNAs were used to generate a stable BeWo B30 trophoblast cell line with reduced MRP5 expression. Control and MRP5‐knockdown cells were treated with vehicle or 8‐Bromo‐cAMP for 24 hr. In response to treatment with 8‐Bromo‐cAMP, the induction of GCM1, hCGa, and hCGb mRNA expression was higher in MRP5 knockdown cells as compared to control cells. Furthermore, MRP5‐knockdown cells were larger in size (including greater numbers of multinucleated cells) and exhibited decreased staining of the tight junction protein E‐cadherin, pointing to enhanced syncytialization. In conclusion, MRP transporters participate in trophoblast cell fusion, which likely represents a novel mechanism regulating placentation and placental toxicities.Support or Funding InformationSupported by F31ES029794, R01ES029275, T32ES007148, P30ES005022.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.