scholarly journals Deoxyribonuclease Is a Potential Counter Regulator of Aberrant Neutrophil Extracellular Traps Formation after Major Trauma

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Meng ◽  
Adnana Paunel-Görgülü ◽  
Sascha Flohé ◽  
Ingo Witte ◽  
Michael Schädel-Höpfner ◽  
...  
Keyword(s):  
Major Trauma ◽  
Neutrophil Extracellular Traps ◽  
Uneventful Recovery ◽  
Trauma Patients ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Extracellular Traps ◽  
Relationship Of ◽  
The Relationship

Introduction. Neutrophil extracellular traps (NET) consist of a DNA scaffold that can be destroyed by Deoxyribonuclease (DNase). Thus DNases are potential prerequisites for natural counter regulation of NETs formation. In the present study, we determined the relationship of NETs and DNase after major trauma.Methods. Thirty-nine major trauma patients, 14 with and 25 without sepsis development were enrolled in this prospective study. Levels of cell-free (cf)-DNA/NETs and DNase were quantified daily from admission until day 9 after admission.Results. Levels of cf-DNA/NETs in patients who developed sepsis were significantly increased after trauma. In the early septic phase, DNase values in septic patients were significantly increased compared to patients without sepsis (P<0.05). cf-DNA/NETs values correlated to values of DNase in all trauma patients and patients with uneventful recovery (P<0.01) but not in septic patients. Recombinant DNase efficiently degraded NETs released by stimulated neutrophils in a concentration-dependent manner in vitro.Conclusions. DNase degrades NETs in a concentration-dependent manner and therefore could have a potential regulatory effect on NET formation in neutrophils. This may inhibit the antibacterial effects of NETs or protect the tissue from autodestruction in inadequate NETs release in septic patients.

scholarly journals Neutrophil Extracellular Traps Activate Proinflammatory Functions of Human Neutrophils

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Dömer ◽  
Tabea Walther ◽  
Sonja Möller ◽  
Martina Behnen ◽  
Tamás Laskay
Keyword(s):  
B Cell ◽  
Adaptive Immune System ◽  
Neutrophil Extracellular Traps ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Extracellular Traps ◽  
Proinflammatory Role

Neutrophil extracellular traps (NETs) consist of decondensed nuclear chromatin that is associated with proteins and are released by neutrophils during an inflammatory response. Released NETs are able to capture pathogens, prevent their dissemination and potentially kill them via antimicrobial peptides and proteins that are associated with the decondensed chromatin. In addition to their antimicrobial functions, NETs have also been shown to exert immunomodulatory effects by activation and differentiation of macrophages, dendritic cells and T cells. However, the effect of NETs on neutrophil functions is poorly understood. Here we report the first comprehensive study regarding the effects of NETs on human primary neutrophils in vitro. NETs were isolated from cultures of PMA-exposed neutrophils. Exposure of neutrophils to isolated NETs resulted in the activation of several neutrophil functions in a concentration-dependent manner. NETs induced exocytosis of granules, the production of reactive oxygen species (ROS) by the NADPH oxidase NOX2, NOX2-dependent NET formation, increased the phagocytosis and killing of microbial pathogens. Furthermore, NETs induced the secretion of the proinflammatory chemokine IL-8 and the B-cell-activating cytokine BAFF. We could show that the NET-induced activation of neutrophils occurs by pathways that involve the phosphorylation of Akt, ERK1/2 and p38. Taken together our results provide further insights into the proinflammatory role of NETs by activating neutrophil effector function and further supports the view that NETs can amplify inflammatory events. On the one hand the amplified functions enhance the antimicrobial defense. On the other hand, NET-amplified neutrophil functions can be involved in the pathophysiology of NET-associated diseases. In addition, NETs can connect the innate and adaptive immune system by inducing the secretion of the B-cell-activating cytokine BAFF.

scholarly journals Antiglycation Activity of Iridoids and Their Food Sources

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Brett J. West ◽  
Akemi Uwaya ◽  
Fumiyuki Isami ◽  
Shixin Deng ◽  
Sanae Nakajima ◽  
...  
Keyword(s):  
Pilot Study ◽  
Food Sources ◽  
Dependent Manner ◽  
Skin Autofluorescence ◽  
Open Label ◽  
Concentration Dependent Manner ◽  
Cross Sectional ◽  
Glycation End Products ◽  
The Relationship

Iridoids are dietary phytochemicals that may have the ability to inhibit the formation of advanced glycation end products (AGEs). Three studies were conducted to investigate this anti-AGE potential. First, the inhibition of fluorescence intensity by food-derived iridoids, after 4 days of incubation with bovine serum albumin, glucose, and fructose, was used to evaluatein vitroantiglycation activity. Next, an 8-week open-label pilot study used the AGE Reader to measure changes in the skin autofluorescence of 34 overweight adults who consumed daily a beverage containing food sources of iridoids. Finally, a cross-sectional population study with 3913 people analyzed the relationship between daily iridoid intake and AGE accumulation, as measured by skin autofluorescence with the TruAge scanner. In thein vitrotest, deacetylasperulosidic acid and loganic acid both inhibited glycation in a concentration-dependent manner, with respective IC50values of 3.55 and 2.69 mM. In the pilot study, average skin autofluorescence measurements decreased by 0.12 units (P<0.05). The cross-sectional population survey revealed that, for every mg of iridoids consumed, there is a corresponding decline in AGE associated age of 0.017 years (P<0.0001). These results suggest that consumption of dietary sources of iridoids may be a useful antiaging strategy.

A study of the in vitro clinical interaction between lidocaine and premedications using rat liver microsomes

2002 ◽  
Vol 21 (8) ◽  
pp. 453-456 ◽  
Author(s):  
A Nagashima ◽  
E Tanaka ◽  
S Inomata ◽  
S Misawa
Keyword(s):  
Liver Microsomes ◽  
Competitive Inhibitor ◽  
Rat Liver Microsomes ◽  
Dependent Manner ◽  
Potential Importance ◽  
Concentration Dependent Manner ◽  
Hepatic Microsomes ◽  
The Relationship ◽  
Substrate Concentrations

In this study, we have investigated the relationship between lidocaine metabolism and premedication, i.e., psychotropic and anti-anxiety agents (diazepam, midazolam), hypnotics (pentobarbital, thiamylal), depolarizing muscular relaxants (vecuronium, pancuronium and suxamethonium), an active anti-hypertensive (clonidine) and an H2 receptor antagonist (cimetidine) using rat hepatic microsomes in vitro. Lidocaine metabolism was noncompetitively inhibited by midazolam (Ki=29.0 mM). Thilamylal was a moderate competitive inhibitor of lidocaine metabolism (Ki=77.8 mM). Pentobarbital, diazepam and cimetidine weakly inhibited lidocaine metabolism formation in a concentration-dependent manner at high substrate concentrations. On the other hand, vecuronium, pancuronium, suxamethonium and clonidine did not inhibit lidocaine metabolism over the therapeutic range. These results show that the interaction between lidocaine and midazolam and thiamylal, catalyzed by a similar cytochrome P450, is of potential importance in toxicological and clinical studies.

Further Characterization of Human Platelet Activation in the Absence of Aggregation: Phosphorylations of Specific Proteins and Relationship with Platelet Secretion

1984 ◽  
Vol 51 (02) ◽  
pp. 198-203 ◽  
Author(s):  
Danièle Nunez ◽  
Sylviane Levy-Toledano
Keyword(s):  
Platelet Activation ◽  
Serotonin Release ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Release Reaction ◽  
Specific Proteins ◽  
Relationship Of ◽  
The Relationship ◽  
Platelet Secretion

SummaryPlatelet aggregation and secretion have been described to be associated with phosphorylation reactions. Thrombasthénie and EDTA-treated control platelets undergo a normal serotonin release in the absence of aggregation. We now studied the phosphorylation of specific proteins associated with platelet secretion. In the presence of ionophore, significant increases occurred in the phosphorylation of two polypeptides of 43,000 and 20,000 molecular weight (P43 and P20) in a concentration dependent manner, and this was accompanied by an increase in the 14C-5HT release. The 32P-labelling of P43 and P20 reaches a peak within 1 min of platelet activation and is followed by a rapid dephosphorylation over the next 2-10 min. While the P20 is identified as the myosin light chain, the identity and the function of the P43 remain unknown.Isoelectric focusing separates 4 proteins from P43 during two dimensional electrophoresis, but only one of them is phosphorylated by A 23187. Chlorpromazine (CPZ) and trifluoperazine (TFP) inhibit the P43 and P20 phosphorylation as well as the 14C- 5HT release in a dose dependent manner. The inhibitory action of the drugs is more pronounced for P43 than for P20, especially when the reactions are carried out at 20° C instead of at 37° C, while the release reaction is still inhibited under these conditions. These results allow different hypotheses for the relationship of phosphorylation-secretion and indicate the importance of one of these proteins (P43) for the release reaction.

scholarly journals Role of neutrophil extracellular traps in radiation resistance of invasive bladder cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Surashri Shinde-Jadhav ◽  
Jose Joao Mansure ◽  
Roni F. Rayes ◽  
Gautier Marcq ◽  
Mina Ayoub ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neutrophil Extracellular Traps ◽  
Polymorphonuclear Neutrophils ◽  
Dependent Manner ◽  
Potential Therapeutic Target ◽  
Extracellular Traps ◽  
Tumor Immune Microenvironment

AbstractRadiation therapy (RT) is used in the management of several cancers; however, tumor radioresistance remains a challenge. Polymorphonuclear neutrophils (PMNs) are recruited to the tumor immune microenvironment (TIME) post-RT and can facilitate tumor progression by forming neutrophil extracellular traps (NETs). Here, we demonstrate a role for NETs as players in tumor radioresistance. Using a syngeneic bladder cancer model, increased NET deposition is observed in the TIME of mice treated with RT and inhibition of NETs improves overall radiation response. In vitro, the protein HMGB1 promotes NET formation through a TLR4-dependent manner and in vivo, inhibition of both HMGB1 and NETs significantly delays tumor growth. Finally, NETs are observed in bladder tumors of patients who did not respond to RT and had persistent disease post-RT, wherein a high tumoral PMN-to-CD8 ratio is associated with worse overall survival. Together, these findings identify NETs as a potential therapeutic target to increase radiation efficacy.

Carbonic anhydrase 2 is a promising predictive factor in cholangiocarcinoma and potential mediator in Metformin treatment

2021 ◽  
Author(s):  
Chaofu Li ◽  
Li Qin ◽  
Jian Huang ◽  
Yu Zhan ◽  
Guanzhen Yu ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Continuous Administration ◽  
Tissue Samples ◽  
Advanced Stages ◽  
Relationship Of ◽  
The Relationship

Abstract Background Cholangiocarcinoma (CCA) is a rare tumor with an aggressive behavior, early diagnosis is impossible as symptoms emerge only in advanced stages. The discovery of a promising biomarker is urgently needed. Carbonic anhydrase 2 (CA2) was found to be dysregulated in diverse cancers, however limited knowledge of CA2 in CCA development was known. Materials and methods CA2 expression was detected both in human and rat thioacetamide (TAA)-induced CCA model by RT-PCR and IHC staining. The relationship of CA2 expression with clinical outcomes was evaluated by univariate and multivariate analyses. CA2 expression changes were also detected both in vivo and in vitro by a potential CA2 inhibitor, Metformin (Met), which was used to inhibit CCA development. Results The level of CA2 expression was increased in biliary lesions with continuous administration of TAA. CA2 was overexpressed in CCA compared with normal tissue samples in rat model and human samples, and correlated significantly with disease progression. Patients with high CA2 expression had a poorer outcome than those without CA2 expression. Met alleviated TAA-induced CCA lesions, and significantly decreased CA2 expression. Colony formation assay showed Met inhibition in CCA cell abilities to form colonies and CA2 expression. CA2 expression was downregulated by Met in a dose- and time-dependent manner in vitro. Conclusions These findings indicate that CA2 is a promising predictive and prognostic factor, and might serve as a potentially novel therapeutic target for human CCA.

scholarly journals SARS-CoV-2 triggered neutrophil extracellular traps (NETs) mediate COVID-19 pathology

2020 ◽  
Author(s):  
Flavio Veras ◽  
Marjorie Pontelli ◽  
Camila Silva ◽  
Juliana Toller-Kawahisa ◽  
Mikhael de Lima ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Tissue Damage ◽  
A549 Cells ◽  
Tracheal Aspirate ◽  
Neutrophil Extracellular Traps ◽  
Dependent Manner ◽  
Extracellular Traps ◽  
Activated Neutrophils ◽  
Tissue Specimens

AbstractSevere COVID-19 patients develop acute respiratory distress syndrome that may progress to respiratory failure. These patients also develop cytokine storm syndrome, and organ dysfunctions, which is a clinical picture that resembles sepsis. Considering that neutrophil extracellular traps (NETs) have been described as an important factors of tissue damage in sepsis, we investigated whether NETs would be produced in COVID-19 patients and participate in the lung tissue damage. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and respective healthy controls were enrolled. NETs concentration was assessed by MPO-DNA PicoGreen assay or by confocal immunofluorescence. The cytotoxic effect of SARS-CoV-2-induced NETs was analyzed in human epithelial lung cells (A549 cells). The concentration of NETs was augmented in plasma and tracheal aspirate from COVID-19 patients and their neutrophils spontaneously released higher levels of NETs. NETs were also found in the lung tissue specimens from autopsies of COVID-19 patients. Notably, viable SARS-CoV-2 can directly induce in vitro release of NETs by healthy neutrophils in a PAD-4-dependent manner. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represent a potential therapeutic target for COVID-19.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

Improved Method for Obtaining of Arctigenin from Arctium Lappa L. and its Antiproliferative Effect on Human Hepatocarcinoma HepG2 Cells

2020 ◽  
Vol 16 (3) ◽  
pp. 358-362
Author(s):  
Renan S. Teixeira ◽  
Paulo H.D. Carvalho ◽  
Jair A.K. Aguiar ◽  
Valquíria P. Medeiros ◽  
Ademar A. Da Silva Filho ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Crude Extract ◽  
Hepg2 Cells ◽  
Liver Carcinoma ◽  
Adhesion Assay ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Arctium Lappa ◽  
Nih 3T3

Background: Arctigenin is a lignan found in Arctium lappa L. (Asteraceae) that displays anti-inflammatory activities. Previous studies showed that the crude extract of A. Lappa has antitumor activity in human liver carcinoma, lung and stomach cancer cells. The aim of this study was to obtain arctigenin from A. lappa L., as well as to evaluate its antiproliferative effects in cells of liver carcinoma (HepG2) and fibroblasts (NIH/3T3). Methods: Arctigenin was obtained from the hydrolysis of arctiin, which was isolated from the crude extract of A. lappa. The effects of arctigenin and arctiin on HepG2 cell viability and cell adhesion were analyzed by MTT method. Adhesion assay was also carried out to evaluate the antitumor activity. Results: Our results showed that the analytical process to obtain arctigenin was fast and easy. In vitro experiments showed that arctigenin (107-269 μM) decreased HepG2 cells viability and did not cause cytotoxicity on NIH/3T3 cells. Arctigenin (27-269 μM) demonstrated anti-adhesion in HepG2 cells in a concentration-dependent manner, when compared with control. Conclusion: These results suggest a promising pharmacological activity for arctigenin as an antiproliferative compound.

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