scholarly journals Elucidating the Function of an Ancient NF-κB p100 Homologue, CrRelish, in Antibacterial Defense

2007 ◽  
Vol 76 (2) ◽  
pp. 664-670 ◽  
Author(s):  
Ze Hua Fan ◽  
Xiao Wei Wang ◽  
Jinhua Lu ◽  
Bow Ho ◽  
Jeak Ling Ding
Keyword(s):  
Time Course ◽  
Horseshoe Crab ◽  
Secondary Infection ◽  
Protein Profile ◽  
Sequence Context ◽  
Living Fossil ◽  
Immune Priming ◽  
Repeated Infection ◽  
The Family

ABSTRACT The family of NF-κB transcription factors essentially regulates immune-related gene expression. Recently, we isolated and characterized the classical NF-κB/inhibitor κB (IκB) homologues from a “living fossil,” the horseshoe crab, Carcinoscorpius rotundicauda. Interestingly, this ancient species also harbors another class I NF-κB p100 homologue, C. rotundicauda Relish (CrRelish). Similar to Drosophila Relish and the mammalian p100, CrRelish contains both the Rel-homology domains (RHD) and the IκB-like domain. In this study, we found that the RHD of CrRelish can recognize horseshoe crab and human κB response elements and activate the downstream reporter in vitro, thereby suggesting the evolutionary conservation of this molecule. Pseudomonas aeruginosa infection transcriptionally upregulates CrRelish, which exhibits a dynamic protein profile over the time course of infection. Surprisingly, secondary infection reinduced an upsurge in CrRelish protein expression to a level which overrode the protein degradation at 12 h postinfection. These observations strongly suggest the involvement of CrRelish in antibacterial defense. Secondary infection causes (i) the maintenance of a favorable expression-competent sequence context of the CrRelish gene and/or (ii) the derepression or stabilization of the CrRelish transcript resulting from the primary infection to enable the more rapid expression and accumulation of the CrRelish protein, reflecting apparent signal/immune priming in a repeated infection.

Correcting a 135-year error: Limulidae Leach, 1819 (Chelicerata, Xiphosura) is the proper authority, not Limulidae Zittel, 1885

2021 ◽  
pp. 1-2
Author(s):  
Philip M. Novack-Gottshall ◽  
Roy E. Plotnick
Keyword(s):  
Horseshoe Crab ◽  
Marine Species ◽  
Limulus Polyphemus ◽  
Junior Synonym ◽  
Living Fossil ◽  
New Family ◽  
The Family ◽  
The World ◽  
Modern Genus

The horseshoe crab Limulus polyphemus (Linnaeus, 1758) is a famous species, renowned as a ‘living fossil’ (Owen, 1873; Barthel, 1974; Kin and Błażejowski, 2014) for its apparently little-changed morphology for many millions of years. The genus Limulus Müller, 1785 was used by Leach (1819, p. 536) as the basis of a new family Limulidae and synonymized it with Polyphemus Lamarck, 1801 (Lamarck's proposed but later unaccepted replacement for Limulus, as discussed by Van der Hoeven, 1838, p. 8) and Xyphotheca Gronovius, 1764 (later changed to Xiphosura Gronovius, 1764, another junior synonym of Limulus). He also included the valid modern genus Tachypleus Leach, 1819 in the family. The primary authority of Leach (1819) is widely recognized in the neontological literature (e.g., Dunlop et al., 2012; Smith et al., 2017). It is also the authority recognized in the World Register of Marine Species (WoRMS Editorial Board, 2021).

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study

1993 ◽  
Vol 69 (01) ◽  
pp. 021-024 ◽  
Author(s):  
Shawn Tinlin ◽  
Sandra Webster ◽  
Alan R Giles
Keyword(s):  
Factor Viii ◽  
Canine Model ◽  
Significant Inhibition ◽  
Human Condition ◽  
Haemophilia A ◽  
Variable Expression ◽  
The Family ◽  
Over Time

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.

The Effect of Heparin vs. Citrate on the Interaction of Platelets with Vascular Graft Materials

1985 ◽  
Vol 54 (04) ◽  
pp. 842-848 ◽  
Author(s):  
Kandice Kottke-Marchant ◽  
James M Anderson ◽  
Albert Rabinovitch ◽  
Richard A Huskey ◽  
Roger Herzig
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Vascular Graft ◽  
Time Course ◽  
Platelet Reactivity ◽  
Polymer Surfaces ◽  
In Vitro Perfusion ◽  
Citrate Anticoagulation ◽  
Platelet Release

SummaryHeparin is known to affect platelet function in vitro, but little is known about the effect of heparin on the interaction of platelets with polymer surfaces in general, and vascular graft materials in particular. For this reason, the effect of heparin vs. citrate anticoagulation on the interaction of platelets with the vascular graft materials expanded polytetrafluoroethylene (ePTFE), Dacron Bionit (DB) and preclotted Dacron Bionit (DB/PC) was studied in a recirculating, in vitro perfusion system. Platelet activation, as shown by a decrease in platelet count, an increase in platelet release and a decrease in platelet aggregation, was observed for all vascular graft materials tested using heparin and was greater for Dacron and preclotted Dacron than for ePTFE. Significant differences between heparin and citrate anticoagulation were seen for platelet release, platelet aggregation and the relative ranking of material platelet-reactivity. However, the trends and time course of platelet activation were similar with both heparin and citrate for the materials tested.

QUALITATIVE AND QUANTITATIVE PHYTOCHEMICAL SCREENING AND IN VITRO ANTIOXIDANT EVALUATION OF PERGULARIA DAEMIA

2018 ◽  
Vol 24 (2) ◽  
Author(s):  
GITA MISHRA ◽  
HEMESHWER KUMAR CHANDRA ◽  
NISHA SAHU ◽  
SATENDRA KUMAR NIRALA ◽  
MONIKA BHADAURIA
Keyword(s):  
Reducing Sugars ◽  
Antioxidant Properties ◽  
Phytochemical Analysis ◽  
Phytochemical Screening ◽  
Qualitative And Quantitative ◽  
The Family ◽  
Ethanolic Extracts ◽  
Antioxidant Evaluation ◽  
In Vitro Antioxidant Activity

Pergularia daemia belongs to the family Asclepiadaceae, known to have anticancer, anti-inflammatory activity. Aim of the present study was to evaluate qualitative and quantitative phytochemical and antioxidant properties of ethanolic extracts of leaf, stem and root parts of P. daemia . Preliminary phytochemical analysis and in vitro antioxidant properties were evaluated by standard methods. The qualitative phytochemical analysis of P. daemia showed presence of flavonoids, tannins, alkaloid, phytosterol, carbohydrate, phenol, saponin, glycosides, terpenoids, steroids proteins and reducing sugars. Quantitative analysis showed polyphenol, flavonoid, flavonone, flavone and flavonol in P. daemia leaves, stem and root in considerable quantity. The in vitro antioxidant activity of P. daemia clearly demonstrated that leaf, stem and root parts have prominent antioxidant properties and was effective in scavenging free radicals.

Temulawak (Curcuma  xanthorrhizaRoxb.) belongs to the family Zingiberaceae, has been empirically used as herbal medicines. The research was aimed to evaluate three promising lines of Temulawak based on their high bioactive contents (xanthorrhizol and curcuminoid) and its in vitro bioactivity (antioxidant and toxicity), and to obtain information on agrobiophysic environmental condition which produced high bioactive compounds. The xanthorrhizol and curcuminoid contents were measured by HPLC. In vitro antioxidant and toxicity were determined by DPPH (1,1-diphenyl-2-picryl-hydrazyl) method and BSLT (Brine Shrimp Lethality Test). The result showed that promising line A produced the highest yield of bioactive and bioactivity, i.e. 0.157 and 0.056 g plant-1of xanthorrizol and curcuminoid respectively. The IC50 of antioxidant activity was 65.09 mg L-1and LC50of toxicity was 69.05 mg L-1. In this study, Cipenjo had the best temulawak performance than two other locations. According to the agrobiophysic parameters, Cipenjo environmental condition was suitable for temulawak cultivation with temperature 28-34 ºC, rainfall ± 223.97 mm year-1 and sandy clay soil. Keywords: antioxidant, curcuminoid, promising lines, temulawak, xanthorrhizol

1970 ◽  
Vol 40 (2) ◽  
Author(s):  
Waras Nurcholis ◽  
Edy Djauhari Purwakusumah ◽  
Mono Rahardjo ◽  
Latifah K. Darusman
Keyword(s):  
Antioxidant Activity ◽  
Bioactive Compounds ◽  
Brine Shrimp ◽  
Clay Soil ◽  
Herbal Medicines ◽  
Environmental Condition ◽  
In Vitro Bioactivity ◽  
The Family ◽  
Promising Line

Temulawak (Curcuma  xanthorrhizaRoxb.) belongs to the family Zingiberaceae, has been empirically used as herbal medicines. The research was aimed to evaluate three promising lines of Temulawak based on their high bioactive contents (xanthorrhizol and curcuminoid) and its in vitro bioactivity (antioxidant and toxicity), and to obtain information on agrobiophysic environmental condition which produced high bioactive compounds. The xanthorrhizol and curcuminoid contents were measured by HPLC. In vitro antioxidant and toxicity were determined by DPPH (1,1-diphenyl-2-picryl-hydrazyl) method and BSLT (Brine Shrimp Lethality Test). The result showed that promising line A produced the highest yield of bioactive and bioactivity, i.e. 0.157 and 0.056 g plant-1of xanthorrizol and curcuminoid respectively. The IC50 of antioxidant activity was 65.09 mg L-1and LC50of toxicity was 69.05 mg L-1. In this study, Cipenjo had the best temulawak performance than two other locations. According to the agrobiophysic parameters, Cipenjo environmental condition was suitable for temulawak cultivation with temperature 28-34 ºC, rainfall ± 223.97 mm year-1 and sandy clay soil. Keywords: antioxidant, curcuminoid, promising lines, temulawak, xanthorrhizol

PDO Rotonda’s Red Eggplant Extract: In vitro Determination of Biological Properties and Minerals Bioaccessibility

2020 ◽  
Vol 16 (1) ◽  
pp. 65-74
Author(s):  
Ortensia Ilaria Parisi ◽  
Mariarosa Ruffo ◽  
Fabio Amone ◽  
Rocco Malivindi ◽  
Domenico Gorgoglione ◽  
...  
Keyword(s):  
Control Sample ◽  
Specific Area ◽  
Biological Properties ◽  
Ammonium Molybdate ◽  
Antihypertensive Activity ◽  
Protected Designation Of Origin ◽  
The Family ◽  
Oil Red O Staining

Background: The Rotonda’s Red Eggplant belongs to the family of Solanum aethiopicum and it is cultivated in a specific area of Potenza (Basilicata, South of Italy) including villages of Rotonda, Viggianello, Castelluccio Superiore and Castelluccio Inferiore. The Red Eggplant cultivated in this area has gained the PDO, “Protected Designation of Origin”. Objective: The aim of this research was to evaluate the use of PDO Rotonda’s Red Eggplant extract as a possible nutraceutical supplement. The antioxidant, antihypertensive, hypoglycemic, and hypolipidemic properties were in vitro evaluated. Methods: The antioxidant activity was investigated by evaluating the scavenging properties against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals and by performing the Ammonium Molybdate and Folin-Ciocalteu assay. The hypoglycemic and antihypertensive activity was studied by evaluating the α-Amylase, α-Glucosidase and Angiotensin Converting Enzyme, respectively, inhibiting activity. In order to evaluate the hypolipidemic activity, the pancreatic lipase inhibiting property was determined and Oil Red O staining assay was performed. Finally, to evaluate the possible use of this extract as a minerals supplement, Selenium, Potassium and Chrome bioaccessibility was studied. Results: The obtained results underline the good antioxidant, hypoglycemic, antihypertensive and hypolipidemic in vitro properties of the PDO Rotonda’s Red Eggplant extract. Moreover, the obtained data show a higher minerals bioaccessibility and this higher value could be ascribable to the natural phytocomplex of PDO Rotonda’s Red Eggplant, which increases the minerals bioaccessibility if compare it with a control sample. Conclusion: The obtained results show that PDO Rotonda’s Red Eggplant extract, might be used as a possible nutraceutical supplement, along with traditional therapies, both for its biological properties and for its minerals bioaccessibility value.

Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine

1985 ◽  
Vol 108 (4) ◽  
pp. 511-517 ◽  
Author(s):  
Nandalal Bagchi ◽  
Birdie Shivers ◽  
Thomas R. Brown
Keyword(s):  
Time Course ◽  
Period 2 ◽  
Iodotyrosine Deiodinase ◽  
Rate Of Hydrolysis ◽  
Underlying Mechanisms ◽  
Excess Iodide ◽  
Sites Of Action ◽  
Hydrolysis Of

Abstract. Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of Nal to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4C1 and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis. Our data are consistent with the hypothesis that excess iodide acutely inhibits thyroglobulin hydrolysis by increasing the resistance of thyroglobulin to proteolytic degradation through increased iodination and coupling.

scholarly journals DDRE-09. DEVELOPING IDO-PROTACS TO IMPROVE IMMUNOTHERAPEUTIC EFFICACY IN PATIENTS WITH GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii63-ii63
Author(s):  
Lakshmi Bollu ◽  
Derek Wainwright ◽  
Lijie Zhai ◽  
Erik Ladomersky ◽  
Kristen Lauing ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Time Course ◽  
Immune Cell ◽  
Enzyme Inhibitors ◽  
Tumor Development ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Specific Protein ◽  
Cell Functions

Abstract INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO; IDO1) is a rate-limiting enzyme that metabolizes the essential amino acid tryptophan into kynurenine. Recent work by our group has revealed that IDO promotes tumor development and suppresses immune cell functions independent of its enzyme activity. Moreover, pharmacologic IDO enzyme inhibitors that currently serve as the only class of drugs available for targeting immunosuppressive IDO activity, fail to improve the survival of patients with GBM. Here, we developed IDO-Proteolysis Targeting Chimeras (IDO-PROTACs). PROTACs bind to a specific protein and recruit an E3 ubiquitin ligase that enhance proteasome-mediated degradation of the target protein. METHODS A library of ≥100 IDO-PROTACs were developed by joining BMS986205 (IDO binder) with a linker group to various E3-ligase ligands. Western blot analysis of PROTAC-induced IDO degradation was tested in vitro among multiple human and mouse GBM cell lines including U87, GBM6, GBM43 and GL261 along a time course ranging between 1–96 hours of treatment and at varying concentrations. The mechanism of IDO protein degradation was investigated using pharmacologic ligands that inhibit or compete with the proteasome-mediated protein degradation pathway. RESULTS Primary screening identified several IDO-PROTACs with IDO protein degradation potential. Secondary screening showed that our lead compound has a DC50 value of ~0.5µM with an ability to degrade IDO in all GBM cells analyzed, and an initial activity within 12 hours of treatment that extended for up to 96 hours. Mutating the CRBN-binding ligand, pretreatment with the ubiquitin proteasome system inhibitors MG132 or MLN4924 or using unmodified parental compound all inhibited IDO protein degradation. CONCLUSIONS This study developed an initial IDO-PROTAC technology that upon further optimization, can neutralize both IDO enzyme and non-enzyme immunosuppressive effects. When combined with other forms of immunotherapy, IDO-PROTACs have the potential to substantially enhance immunotherapeutic efficacy in patients with GBM.

scholarly journals Time Course of Early Events in the Action of Glucocorticoids on Rat Thymus Cells in Vitro

1973 ◽  
Vol 248 (8) ◽  
pp. 2922-2927
Author(s):  
Cornelius Hallahan ◽  
Donald A. Young ◽  
Allan Munck
Keyword(s):  
Time Course ◽  
Thymus Cells
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