Abstract 212: Prophylactic Anti-inflammatory Treatment Attenuates The Neuroinflammatory And Behavioral Effects Of Silent Cerebral Infarction

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Christina L Nemeth ◽  
Gretchen N Neigh
Keyword(s):  
Gene Expression ◽  
Cardiac Surgery ◽  
Open Field ◽  
Treatment Strategies ◽  
Fold Change ◽  
Inflammatory Activity ◽  
Central Tendency ◽  
Negative Consequences ◽  
Anti Inflammatory

Silent brain infarction is a frequent complication of cardiac surgery and is associated with mood changes and cognitive disruption. Microsphere embolism (ME) rodent models recapitulate both the diffuse ischemic infarcts and the delayed subtle behavioral disturbances characteristic to silent infarction (SI). Previously, we have shown that ME leads to increased hippocampal inflammation, weakening of the blood brain barrier, and the infiltration of peripherally circulating inflammatory cells in rats. Given long-term increases in inflammatory activity following SI, the current study tests the efficacy of anti-inflammatory versus anti-depressant treatment strategies to reduce the inflammatory and behavioral sequelae of injury. Adult rats were administered either chronic meloxicam (preferential COX-2 inhibitor) or fluoxetine (SSRI) beginning five days prior to ME surgeries. After a two week recovery, animals were tested for anxiety-like behaviors in the open field paradigm and the hippocampus was examined for gene expression of inflammatory cytokines. Meloxicam treated animals showed a decrease in hippocampal gene expression of inflammatory markers (SPP1; p = 0.0272) and greater than a 3-fold change improvement in open field central tendency (p = 0.0003). No differences in inflammatory gene expression were observed in fluoxetine treated animals (SPP1; p = 0.3288); however, fluoxetine treatment resulted in a 2-fold change improvement in open field central tendency (p = 0.0138) suggesting that while both treatment strategies attenuate SI induced behavioral disruption, only meloxicam acts via inflammatory mechanisms. Given the long term negative consequences of increased central and peripheral inflammatory activity, the data suggest that anti-inflammatory therapeutic strategies may benefit patients at risk for SI as well as cardiac surgery candidates.

scholarly journals The impact of androgen receptor (AR) and histone deacetylase 1 (HDAC1) expression on the prognosis of ductal carcinoma in situ (DCIS)

2020 ◽  
Author(s):  
Choong Man Lee ◽  
Jisun Kim ◽  
Yang Soon Park ◽  
Gyung Won Yoon ◽  
Hwi Gyeong Jo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Androgen Receptor ◽  
Histone Deacetylase ◽  
Gene Expression Analysis ◽  
Ductal Carcinoma ◽  
External Validation ◽  
Fold Change ◽  
Histone Deacetylase 1

Abstract Background Ductal carcinoma in situ (DCIS) display favorable outcome but little is known about the factors associated with invasive recurrence. To identify better prognostic biomarkers, we performed gene expression analysis followed by immunohistochemistry (IHC) staining validation. Methods Differential gene expression (DGE) analysis of 24 pure DCIS patients was performed using a nanostring platform. RNA was extracted from paraffin blocks from age/estrogen receptor matched recurrence-free (n=16) and invasive-recurrence (n=8) cases (disease-free interval >5 years). External validation was done among independent 61 cases, invasive-recurrence (n=16) and recurrence-free (n=45) pure DCIS cases by IHC staining. Results Eight differentially expressed genes were found statistically significant (log 2-fold change <–1 or >1 and p<0.001). Less than ½ fold expression of CUL1, AR, RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes were observed in REC cases compared to NED cases. Androgen receptor (AR) and histone deacetylase 1 (HDAC1) were selected for external validation (AR: log 2-fold change –1.35, p<0.001, and HDAC1; log 2-fold change –0.774, p<0.001). AR and HDAC1 protein expression was externally validated by IHC staining of 61 pure DCIS cases (16 invasive-recurrence versus 45 recurrence-free). Absence of AR and high HDAC1 expression was an independent risk factor for invasive recurrence (hazard ratio 5.04, 95% CI: 1.24, 20.4; p=0.023, hazard ratio 3.07, 95% CI: 1.04, 9.04; p=0.042). High nuclear grade (NG 3) was also associated with long term invasive recurrence. Conclusion Comparative gene expression analysis of pure DCIS revealed 8 genes differentially expressed among recurred cases. Immunohistochemistry validation within an independent cohort suggests that, absence of AR and overexpression of HDAC1 was associated with greater risk of long term invasive recurrence among pure DCIS.

Anti-nociceptive and anti-inflammatory activity of synthesized novel benzoxazole derivatives

2021 ◽  
Vol 20 ◽  
Author(s):  
Mansi L. Patil ◽  
Swati S. Gaikwad ◽  
Naresh J. Gaikwad
Keyword(s):  
Cytotoxic Activity ◽  
Research Study ◽  
Ex Vivo ◽  
Immunological Response ◽  
Inflammatory Activity ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Introduction: Pain is an immunological response to any infection or inflammation and long term use of pain management therapy includes use of Nonsteroidal anti-inflammatory drugs which is associated with occurrence of toxicity as well as gastrointestinal bleeding. Therefore, the investigation of new analgesic and anti-inflammatory agents remains a major challenge. Aims: The objective of this research study is to undergo the pharmacological evaluation of newly synthesized benzoxazole derivatives. These novel derivatives were evaluated for anti-nociceptive, anti-inflammatory and cytotoxic activity using various in-vivo and ex-vivo methods. Methods: The study was carried out using swiss mice (adult male) weighing between 20gm to 30gm and were divided into groups containing (n=6) six animals in each group for treatment. The anti-nociceptive activity was performed by using 0.1ml of 0.6% v/v acetic acid as nociception inducer and evaluated by the diminished number of abdominal writhes. The anti-inflammatory activity was done using 0.1 ml of 2% w/v Carrageenan induced paw edema method was observed which was evaluated by calculating the percent maximum possible effect. Histopathological evaluation and cytotoxic activity of the compounds was carried out. Results: The results of this research study revealed that synthesized derivatives (a, b, c, d and e) showed promising anti-nociceptive and anti-inflammatory effect along significantly higher cytotoxic activity in MCF-7 cell lines. Conclusion: It can be concluded that synthesized derivatives (a, b, c, d and e) have potential anti-nociceptive and anti-inflammatory effect along with cytotoxic activity and certain modification in structure may result in potent activity.

scholarly journals Statin Therapy in Post-Operative Atrial Fibrillation: Focus on the Anti-Inflammatory Effects

2021 ◽  
Vol 8 (3) ◽  
pp. 24
Author(s):  
Homa Nomani ◽  
Amir Hooshang Mohammadpour ◽  
Željko Reiner ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Atrial Fibrillation ◽  
Cardiac Surgery ◽  
Safety Concern ◽  
Artery Bypass ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
High Dose ◽  
Increased Risk ◽  
Effective Option ◽  
Anti Inflammatory

Background: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in long-term use. Therefore, more appropriate treatment strategies are needed. Methods: In this paper, the efficacy, safety, and other aspects of using statins in the prevention of POAF focusing on their anti-inflammatory effects are reviewed. Results: Recent studies have suggested that inflammation has a significant role in POAF, from the first AF episode to its serious complications including stroke and peripheral embolism. On the other hand, statins, the most widely used medications in cardiovascular patients, have pleiotropic effects, including anti-inflammatory properties. Therefore, they may potentially be effective in POAF prevention. Statins, especially atorvastatin, appear to be an effective option for primary prevention of POAF, especially in patients who had coronary artery bypass grafting (CABG), a cardiac surgery treatment associated with inflammation in the heart muscle. However, several large studies, particularly with rosuvastatin, did not confirm the beneficial effect of statins on POAF. One large clinical trial reported higher risk of acute kidney injury (AKI) following high-dose rosuvastatin in Chinese population. In this study, rosuvastatin reduced the level of C-reactive protein (CRP) but did not reduce the rate of POAF. Conclusion: Further studies are required to find the most effective statin regimen for POAF prevention with the least safety concern and the highest health benefits.

scholarly journals Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD

2018 ◽  
Vol 4 (4) ◽  
pp. 00031-2018 ◽  
Author(s):  
Katherine J. Baines ◽  
Thomas K. Wright ◽  
Peter G. Gibson ◽  
Heather Powell ◽  
Philip M. Hansbro ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Low Dose ◽  
T Cell Responses ◽  
T Test ◽  
Fold Change ◽  
Differentially Expressed ◽  
Cell Responses ◽  
Paired T Test

Long-term, low-dose azithromycin reduces exacerbation frequency in chronic obstructive pulmonary disease (COPD), yet the mechanism remains unclear. This study characterised genome-wide gene expression changes in patients with neutrophilic COPD following long-term, low-dose azithromycin treatment.Patients with neutrophilic COPD (>61% or >162×104 cells per mL sputum neutrophils) were randomised to receive either azithromycin or placebo for 12 weeks. Sputum and blood were obtained before and after 12 weeks of treatment. Gene expression was defined using microarrays. Networks were analysed using the Search Tool for the Retrieval of Interacting Gene database.In sputum, 403 genes were differentially expressed following azithromycin treatment (171 downregulated and 232 upregulated), and three following placebo treatment (one downregulated and two upregulated) compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.5). In blood, 138 genes were differentially expressed with azithromycin (121 downregulated and 17 upregulated), and zero with placebo compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.3). Network analysis revealed one key network in both sputum (14 genes) and blood (46 genes), involving interferon-stimulated genes, human leukocyte antigens and genes regulating T-cell responses.Long-term, low-dose azithromycin is associated with downregulation of genes regulating antigen presentation, interferon and T-cell responses, and numerous inflammatory pathways in the airways and blood of neutrophilic COPD patients.

scholarly journals Anti-inflammatory Activity of Jurubeba (Solanum paniculatum L.) Through Reducing the T-bet and GATA3 Gene Expression, In Vitro

2017 ◽  
Vol 139 (2) ◽  
pp. AB268 ◽  
Author(s):  
Raimon Rios ◽  
Hugo Bernardino Ferreira Silva ◽  
Norma Vilany Queiroz Carneiro ◽  
Ryan Santos Costa ◽  
Tamires Cana Brasil Carneiro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Activity ◽  
Anti Inflammatory

scholarly journals Long-Lasting Anti-Inflammatory Activity of Human Microfragmented Adipose Tissue

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Sara Nava ◽  
Valeria Sordi ◽  
Luisa Pascucci ◽  
Carlo Tremolada ◽  
Emilio Ciusani ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Activity ◽  
Tissue Cell ◽  
Single Shot ◽  
Term Survival ◽  
Long Term Survival ◽  
Anti Inflammatory

Over the last few years, human microfragmented adipose tissue (MFAT), containing significant levels of mesenchymal stromal cells (MSCs) and obtained from fat lipoaspirate (LP) through a minimal manipulation in a closed system device, has been successfully used in aesthetic medicine as well as in orthopedic and general surgery. Interestingly, in orthopedic diseases, this ready-to-use adipose tissue cell derivative seems to have a prolonged time efficacy even upon a single shot injection into osteoarthritic tissues. Here, we investigated the long-term survival and content of MSCs as well the anti-inflammatory activity of LP and its derived MFAT in vitro, with the aim to better understand a possible in vivo mechanism of action. MFAT and LP specimens from 17 human donors were investigated side by side. During a long-term culture in serum-free medium, we found that the total cell number as well the MSC content in MFAT decreased more slowly if compared to those from LP specimens. The analysis of cytokines and growth factors secreted into the conditioned medium (CM) was similar in MFAT and LP during the first week of culture, but the total amount of cytokines secreted by LP decreased much more rapidly than those produced by MFAT during prolonged culture (up to 28 days). Similarly, the addition of MFAT-CM recovered at early (3-7 days) and late stage (14-28 days) of culture strongly inhibited inflammatory function of U937 monocyte cell line, whereas the anti-inflammatory activity of LP-CM was drastically reduced after only 7 days of culture. We conclude that MFAT is an effective preparation with a long-lasting anti-inflammatory activity probably mediated by a long-term survival of their MSC content that releases a combination of cytokines that affect several mechanisms involved in inflammation processes.

scholarly journals ESTIMATION OF ANTI-INFLAMMATORY ACTIVITY AS WELL AS APOPTOTIC ACTIVITY OF ETHANOLIC EXTRACTS OF CROCUS SATIVUS

2019 ◽  
Author(s):  
B. Arirudran ◽  
P. Priyadharshini ◽  
US Mahadeva Rao
Keyword(s):  
Gene Expression ◽  
Oxidative Burst ◽  
Phagocytic Activity ◽  
Vascular Diseases ◽  
Inflammatory Activity ◽  
Crocus Sativus ◽  
Rt Pcr ◽  
Ethanolic Extracts ◽  
Anti Inflammatory ◽  
Apoptotic Activity

Inflammation is a body reaction which embroils cellular and biochemical responses, which is not only symptom for shared diseases but also known to be an initial phase for certain serious Alzheimer’s, cancer, heart vascular diseases. In order to overcome these drawbacks, there is an urgent need for nutraceuticals with excellent anti-inflammatory response with minimum side effects. Aim: An attempt has been made to evaluate the anti-inflammatory activity along with gene expression analysis on ethanolic extracts of Crocus sativus (CSEE). Dried stigmas of C. sativus were analyzed for anti-inflammatory activity by macrophage scavenging assay. In this study, the phagocytic activity of the extract was tested on oxidative burst reduction of macrophages. RT-PCR was performed to analyze the anti-apoptotic gene expression during cell death, as a result of the compound treatment on cancer cells. The CSEE unveiled high phagocytic activity on the oxidative burst reduction, presenting intracellular killing and the enhancement of lysosomal enzyme activity, showing the active degranulation of macrophages. These findings suggest that C. sativus possessed excellent anti-inflammatory as well as apoptotic activities. Hence it was proposed that C. sativus could be exploited against oxidative stress, anti-inflammatory, cancer and ageing therapy to justify their use in traditional medicine as a nutraceutical.

scholarly journals Two New Iridoid Glucosides from the Whole Plant of Patrinia scabiosifolia Link

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4201
Author(s):  
Shikai Sun ◽  
Jiang Fu ◽  
Kaidong Liu ◽  
Mingzhu Dai ◽  
Yong Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
2D Nmr ◽  
Inflammatory Activity ◽  
Spectroscopic Analyses ◽  
Whole Plant ◽  
Phytochemical Investigation ◽  
Iridoid Glucosides ◽  
Anti Inflammatory ◽  
Whole Plants

As a traditional Chinese medicine, Patrinia scabiosifolia Link has been used to treat various inflammatory-related diseases, and recent studies have shown that it possesses potent anti-inflammatory activity. Therefore, phytochemical investigation on whole plants of P. scabiosifolia were carried out, which led to the isolation of two new iridoid glucosides, patriniscabiosides A (1) and B (2), together with six known compounds (3–8). The structural elucidation of all compounds was performed by HRESIMS and extensive spectroscopic analyses including IR, 1D, 2D NMR, and electronic circular dichroism (ECD). All the isolated compounds were tested for their anti-inflammatory activity using the NF-κB-Dependent Reporter Gene Expression Assay, and compound 3 displayed anti-inflammatory activity through the inhibition of the NF-κB pathway, with an inhibitory rate of 73.44% at a concentration of 10 μM.

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