Abstract P430: Inflammatory Survival Gene Expression Patterns Differentiate Favorable and Unfavorable Outcomes Following Surgical Intervention in Intracerebral Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ifeanyi O Iwuchukwu ◽  
doan nguyen ◽  
Jasmine Warren ◽  
ALIREZA SHIRAZIAN ◽  
Vi Tran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Surgical Management ◽  
Expression Patterns ◽  
Early Time ◽  
Pcr Analysis ◽  
Early Time Point ◽  
Time Points ◽  
Arginase 1 ◽  
Anti Inflammatory ◽  
Time Point

Background and Aims: Surgical management of intracerebral (ICH) remains controversial due to unclear benefit. In this study, we analyzed temporal changes in expression of proinflammatory and anti-inflammatory survival genes to discern the molecular differences between favorable and unfavorable outcomes after surgery. Methods: Venous blood collected in Paxgene Blood RNA from ICH patients before surgery at ‘early’ (Day 0-2) and at ‘delayed’ (Day 3-5) timepoints. Extracted total RNA was used for real-time Taqman PCR analysis for anti-inflammatory, survival genes superoxide dismutase 1(SOD1), COX-2, IL-10, peroxisome proliferator activated receptor gamma (PPARG), TGF-B1, and IL-10. The pro-inflammatory genes included arginase-1 (ARG1), TNF, IL-1B, monocyte/macrophage activity markers (CD36, CD163) and NF-kB members (NFKB1, NFKB2, RELA, RELB, REL, NFKBIA). Relative fold changes were determined after normalizing to GAPDH. 90-day Modified Rankin Score (mRS) were collected and classified as favorable, mRS 0-3 (n=4) and unfavorable, mRS 4-6 (n=8). Statistical analysis was carried out by Welch’s ANOVA test (p<0.05). Results: Mean age was 56.25yrs (SD 19.7). ICH location was 10 deep nuclei (thalamus or basal ganglia), 1 cerebellum, and 1 lobar. ICH volume was lower in the mRS 0-3 group (24.15ml SD21.2 vs 35.8ml SD 31.7 p=0.68). All patients had a decompressive hemicraniectomy and 7 included hematoma evacuation. Overall, the NFkB family gene expression was increased at ‘delayed’ relative to the early time points in both groups. However, RELB expression was significantly higher at the early time point of mRS 0-3 compared to mRS 4-6 group. Expression of ARG1, SOD1, COX2, IL-1B, IL-10, TGF-B1, PPARG and CD36 increased significantly at the delayed compared to the early time point. In the unfavorable outcome group (mRS 4-6), TNF expression increased significantly at the delayed timepoints compared to mRS 0-3 which was unchanged. Conclusions: The studied genes were highly expressed and differed significantly between time points. TNF was significantly expressed at the delayed time point in the mRS 4-6 group but unchanged in the mRS 0-3 group. Further studies will explore the role of TNF and related genes in patient selection and outcomes for surgical management of ICH.

scholarly journals Quantitative Real-Time RT—PCR Analysis of Inflammatory Gene Expression Associated with Ischemia—Reperfusion Brain Injury

2002 ◽  
Vol 22 (9) ◽  
pp. 1068-1079 ◽  
Author(s):  
Rossana Berti ◽  
Anthony J. Williams ◽  
John R. Moffett ◽  
Sarah L. Hale ◽  
Luisa C. Velarde ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Injury ◽  
Real Time ◽  
Adhesion Molecules ◽  
Ischemia Reperfusion ◽  
Fold Increase ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Time Points ◽  
Time Point

Ischemia-reperfusion brain injury initiates an inflammatory response involving the expression of adhesion molecules and cytokines, some of which are regulated by the nuclear transcription factor NF-κB. In this study the authors examined mRNA expression levels for several important genes associated with inflammation at five time points (3, 6, 12, 24, and 72 hours) after transient middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. A sensitive and quantitative technique (TaqMan real-time QRT-PCR) was used to simultaneously measure mRNA levels for key cell adhesion molecules and inflammatory cytokines. Gene expression increased significantly in the injured hemisphere for interleukin (IL)-1β (12-fold increase at 24 hours), IL-6 (25-fold increase at 6 hours) and ICAM-1 (4-fold increase at 24 hours), and the in-terhemispheric differences for these genes were significant for every time point examined ( P < 0.05 for all values). Tumor necrosis factor-α mRNA was upregulated in the injured versus uninjured hemisphere from 3 to 24 hours (5-fold increase at 6 hours), while E-selectin showed a significant increase in mRNA levels from 6 to 24 hours after MCAO (10-fold increase at 6 hours) ( P < 0.05 for all values). VCAM-1 mRNA levels did not respond differentially to injury at any time point between the two brain hemispheres. At all time points examined, activated NF-κB immunoreactivity was observed in cells throughout the infarct-damaged tissue. These results are consistent with the proinflammatory properties of the induced molecules, which are involved in the initiation of the inflammatory cascade, and may thus contribute to secondary cellular responses that lead to further brain damage.

scholarly journals Comprehensive Comparison of Amnion Stromal Cells and Chorion Stromal Cells by RNA-Seq

2021 ◽  
Vol 22 (4) ◽  
pp. 1901
Author(s):  
Brielle Jones ◽  
Chaoyang Li ◽  
Min Sung Park ◽  
Anne Lerch ◽  
Vimal Jacob ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Principal Component ◽  
Differentially Expressed ◽  
Inflammatory Factor ◽  
Next Generation Sequencing Technology ◽  
Angiogenic Potential ◽  
Anti Inflammatory

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.

Abstract 456: Myxoma Viral Proteins, M-T7, Serp-1 and Serp-2, Alter Human Monocyte Gene Expression in Vitro

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Jennifer Davids ◽  
Mee Y Bartee ◽  
Richard W Moyer ◽  
Alexandra R Lucas
Keyword(s):  
Gene Expression ◽  
Animal Models ◽  
Arterial Occlusion ◽  
Viral Proteins ◽  
Immune Defense ◽  
Pcr Analysis ◽  
Monocytic Cells ◽  
Plaque Growth ◽  
Anti Inflammatory ◽  
Significant Expression

Introduction: Atherosclerosis is characterized by ongoing chronic inflammation, cell damage, apoptosis and scar formation all of which can initiate plaque growth and arterial occlusion. These proteases are controlled by serine protease inhibitors, or serpins, which regulate apoptotic and inflammatory pathways. Complex DNA viruses, such as myxomavirus, have developed highly active immune defense systems which include viral serpins that inhibit inflammation at picogram to microgram doses. Serp-1, a secreted serpin, significantly reduces inflammatory cell activation, invasion and plaque growth in animal models and is in clinical trials. One cross-class serpin, Serp-2, has demonstrated anti-inflammatory and anti-apoptotic effects in a variety of animal models. M-T7, a secreted non-serpin chemokine binding protein, reduces vascular plaque and inflammation. Previous microarray experiments detected no significant changes with viral protein treatment alone, underscoring a need for activated cells. This study assesses the effects of viral proteins with anti-inflammatory and anti-atherogenic activity on atherosclerosis-related gene expression changes in activated human monocytes. Methods: Triplicate samples of THP-1 human monocytic cells were incubated with saline, 10μM camptothecin alone or in combination with individual serpins (500ng/million cells) for 30 mins at 37°C. Real-time RT-PCR analysis was performed. Results: At 30m, the viral proteins elicited significant expression changes in THP-1 monocytes for genes in purported atherosclerotic pathways. CCL2 was upregulated by Serp-1 (P = 0.0031). PDGFB was significantly increased by Serp-1 (P = 0.0203) and to a lesser extent by Serp-2 and M-T7. M-T7 significantly upregulated L-Selectin (P = 0.0023). Serp-2 significantly downregulated Lipoprotein(a) (P =0.0500). Conclusion: Significant expression changes were detected in human monocytic cells after treatment with three unique anti-inflammatory viral proteins. Differential regulation of genes such as PDGFB underscores the multifaceted approach viral proteins take toward controlling inflammation. Altering atherogenic responses in monocytic cells represents a new potential therapeutic target for inflammatory vascular diseases.

Effect of Analgesic Drugs on Tooth Sensitivity Induced by In-office Dental Bleaching: A Systematic Review and Meta-analysis

2020 ◽  
Vol 45 (2) ◽  
pp. E66-E76 ◽  
Author(s):  
RTF Costa ◽  
SLD Moraes ◽  
CAA Lemos ◽  
JR SoutoMaior ◽  
BC do E Vasconcelos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Drug Group ◽  
Preemptive Analgesia ◽  
Tooth Bleaching ◽  
Tooth Sensitivity ◽  
Time Points ◽  
Significant Difference ◽  
Anti Inflammatory ◽  
Time Point

SUMMARY Objective: This systematic review evaluates the effect of preemptive analgesia on tooth sensitivity induced by in-office tooth bleaching. Methods: The review was structured based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. The methods were recorded at PROSPERO (CRD42018095440). Randomized clinical trials, studies published in English, and studies in which the efficacy of preemptive analgesia with analgesic and anti-inflammatory medications prior to in-office tooth bleaching was compared with that of placebo were included. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library were used for searching. The electronic search provided 373 articles, and seven of them were selected based on the inclusion criteria. Results: Immediately after time point, a significant reduction of dental sensitivity was observed in the drug group compared to the control group (p=0.02; mean difference [MD]: −0.90; confidence interval [CI]: −1.63 to −0.16), while there was no significant difference at up to one-hour (p=0.22; MD: −0.42; CI: −1.09 to −0.25), at 1-24–hour (p=0.88; MD: −0.05; CI: −0.61 to 0.72), or 24-48–hour (p=0.69; MD: 0.05; CI: −0.21 to 0.32) time points. The incidence of sensitivity during the procedure was not statistically different between the groups (p=0.64; MD: 0.91; CI: 0.92 to 1.15). The nonsteroidal anti-inflammatory drug group showed a statistically significant reduction (p=0.04; MD: −0.69; CI: −1.36 to −0.03) in tooth sensitivity compared with the other groups. Conclusions: This systematic review and meta-analysis demonstrated that the medications analyzed did not interfere with the incidence of sensitivity symptoms. Regarding the intensity, no difference was observed between the drug and placebo groups at the up to one-hour, 1-24–hour, or 24-48–hour time points, and there was a statistically significant difference at the zero-hour time point in favor of the drug group. However, based on the variables that influenced this result, it should be considered with prudence because a small difference was observed.

Cranioplasty Reverses Dysfunction of the Solutes Distribution in the Brain Parenchyma After Decompressive Craniectomy

Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 1064-1069 ◽  
Author(s):  
Alin Borha ◽  
Audrey Chagnot ◽  
Romain Goulay ◽  
Evelyne Emery ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Decompressive Craniectomy ◽  
Early Time ◽  
Brain Parenchyma ◽  
Late Time ◽  
Perivascular Spaces ◽  
Early Time Point ◽  
The Impact ◽  
The Brain ◽  
Brain Homeostasis ◽  
Time Point

Abstract Background Solutes distribution by the intracranial cerebrospinal fluid (CSF) fluxes along perivascular spaces and through interstitial fluid (ISF) play a key role in the clearance of brain metabolites, with essential functions in maintaining brain homeostasis. Objective To investigate the impact of decompressive craniectomy (DC) and cranioplasty (CP) on the efficacy of solutes distribution by the intracranial CSF and ISF flux. Methods Mice were allocated in 3 groups: sham surgery, DC, and DC followed by CP. The solutes distribution in the brain parenchyma was assessed using T1 magnetic resonance imaging after injection of DOTA-Gadolinium in the cisterna magna. This evaluation was performed at an early time point following DC (after 2 d) and at a later time point (after 15 d). We evaluated the solutes distribution in the whole brain and in the region underneath the DC area. Results Our results demonstrate that the global solutes distribution in the brain parenchyma is impaired after DC in mice, both at early and late time-points. However, there was no impact of DC on the solutes distribution just under the craniectomy. We then provide evidence that this impairment was reversed by CP. Conclusion The solute distribution in the brain parenchyma by the CSF and ISF is impaired by DC, a phenomenon reversed by CP.

Salt induced programmed cell death in rice: evidence from chloroplast proteome signature

2021 ◽  
Vol 48 (1) ◽  
pp. 8
Author(s):  
Vivek Ambastha ◽  
Sudhir K. Sopory ◽  
Baishnab C. Tripathy ◽  
Budhi Sagar Tiwari
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Early Time ◽  
Biological Functions ◽  
Rice Seedlings ◽  
Early Time Point ◽  
Phosphorylation Pattern ◽  
Moderate Salinity ◽  
Chloroplast Proteome ◽  
Time Point

Soil salinity, depending on its intensity, drives a challenged plant either to death, or survival with compromised productivity. On exposure to moderate salinity, plants can often survive by sacrificing some of their cells ‘in target’ following a route called programmed cell death (PCD). In animals, PCD has been well characterised, and involvement of mitochondria in the execution of PCD events has been unequivocally proven. In plants, mechanistic details of the process are still in grey area. Previously, we have shown that in green tissues of rice, for salt induced PCD to occur, the presence of active chloroplasts and light are equally important. In the present work, we have characterised the chloroplast proteome in rice seedlings at 12 and 24 h after salt exposure and before the time point where the signature of PCD was observed. We identified almost 100 proteins from chloroplasts, which were divided in to 11 categories based on the biological functions in which they were involved. Our results concerning the differential expression of chloroplastic proteins revealed involvement of some novel candidates. Moreover, we observed maximum phosphorylation pattern of chloroplastic proteins at an early time point (12 h) of salt exposure.

scholarly journals Equivalent tumor detection for early and late FAPI-46 PET acquisition

2021 ◽  
Author(s):  
J. Ferdinandus ◽  
L. Kessler ◽  
N. Hirmas ◽  
M. Trajkovic-Arsic ◽  
R. Hamacher ◽  
...  
Keyword(s):  
Early Time ◽  
Tumor Detection ◽  
University Hospital ◽  
Late Time ◽  
Early Time Point ◽  
Positron Emission ◽  
Organ Uptake ◽  
Significant Difference ◽  
Late Time Point ◽  
Time Point

Abstract Introduction Positron emission tomography (PET) using small ligands of the fibroblast activation protein (FAP) was recently introduced. However, optimal uptake time has not been defined yet. Here, we systematically compare early (~ 10 min p.i.) and late (~ 60 min p.i.) FAPI-46 imaging in patients with various types of cancer. Methods This is a retrospective single-institutional study. Imaging was performed at the Essen University Hospital, Germany. A total of 69 patients who underwent dual time-point imaging for either restaging (n = 52, 75%) or staging (n = 17, 25%) of cancer were included. Patients underwent PET with two acquisitions: early (mean 11 min, SD 4) and late (mean 66 min, SD 9). Mean injected activity was 148 MBq (SD 33). Results In total, 400 lesions were detected in 69 patients. Two of 400 (0.5%) lesions were only seen in early time-point imaging but not in late time-point imaging. On a per-patient level, there was no significant difference between SUVmax of hottest tumor lesions (Wilcoxon: P = 0.73). Organ uptake demonstrated significant early to late decrease in SUVmean (average ∆SUVmean: − 0.48, − 0.14, − 0.27 for gluteus, liver, and mediastinum, respectively; Wilcoxon: P < 0.001). On a per-lesion basis, a slight increase of SUVmax was observed (average ∆SUVmax: + 0.4, Wilcoxon: P = 0.03). Conclusion In conclusion, early (~ 10 min p.i.) versus late (~ 60 min p.i.) FAPI-46 imaging resulted in equivalent lesion uptake and tumor detection. For improved feasibility and scan volume, we implement early FAPI-46 PET in future clinical and research protocols.

Analysis of Serial Patient Samples Reveals a Variety of Clonal Dynamics In Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1923-1923
Author(s):  
Jonathan J Keats ◽  
Esteban Braggio ◽  
Scott Van Wier ◽  
Patrick Blackburn ◽  
Angela Baker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Leukemia ◽  
Advisory Committees ◽  
Tumor Mass ◽  
Time Points ◽  
Tumor Genome ◽  
Time Point

Abstract Abstract 1923 Our understanding of the genetic abnormalities associated with the development of multiple myeloma has increased significantly in the last decade. However, very little is known about how, or if, myeloma tumor genomes change with time and if therapeutic interventions influence these events. To address these issues we studied a cohort of 29 patients for whom at least two serial samples (1-65 months, median 19 months) were available for analysis. Each serial pair was analyzed by both array-based comparative genomic hybridization (aCGH) and microarray gene expression profiling (GEP) to identify DNA copy number abnormalities (CNA) at a 25kb resolution and gene expression differences present in the bulk of the tumor mass. Though this does not address the intra-clonal heterogeneity that may exist at a given time point, it does answer if the bulk of the tumor mass is changing with time. This study has unearthed several surprising and clinically relevant findings. First, myeloma tumor genomes are not as unstable as previous cytogenetic analyses suggest. In 40% of patients we observed no detectable CNA changes (1-37 months, median 12 months). In 24% of patients we observed the exclusive acquisition of new CNA (1-12, median 3.5) (3-22 months, median 18 months). In 36% of patients we observed both the loss (1-20, median 3) and gain (1-33, median 21) of CNA (5-43 months, median 20 months). Because time was not a significant influence on the detection of stable or unstable genomes we compared CNA changes with TC class and found patients with the high-risk 4p16 and maf IgH translocations were over-represented in the latter subset of patients. These observations raise the question of what happens between multiple rounds of therapy and if different regimens influence these phenotypes differently. For two patients with no CNA changes between the first two time points there was an additional sample that extended the follow-up by 52 and 12 months. Again no CNA changes were seen between diagnosis and these final samples taken 63 and 50 months later. For one patient with CNA changes (5 shared, 29 lost, and 32 gained) we have a detailed time course of 5 samples from diagnosis through to end-stage plasma cell leukemia. This patient received continuous lenalidomide-dexamethasone (Rd) for 20 months and progessed with a clone containing a BIRC2/3 deletion, which activates the NFKB pathway. The patient received single agent PR-171 and a bortezomib containing regimen and unexpectedly, the tumor genome observed in the third sample was almost identical (32 shared, 2 lost, and 4 gained CNA) to the first time point, including two copies of BIRC2/3. Subsequently, the patient received melphalan-prednisone-bortezomib (MPV) and the tumor genome observed in the fourth and fifth samples, which were identical, were similar to that seen in the second sample (24 shared, 13 lost, and 39 gained CNA). To understand these observations better we performed FISH to ascertain if the observed clones were detectable earlier, albeit at a low frequency. These experiments proved that the two dominant subclones observed at time points 1 and 3 versus 2, 4, 5 were mutually exclusive at the single cell level. Moreover, both of these clones were detectable at diagnosis with 12% of the tumor mass being the second subclone that eventually evolved into plasma cell leukemia. Interestingly, we assayed 5 of the 39 unique CNA observed in the final two samples and only one, the 17p13 deletion, was detectable earlier. This suggests the MPV regimen effectively eliminated a clone that was previously sensitive to Rd and selected for a dramatically evolved subclone that was previously sensitive to two different proteasome inhibitors. Although it is clear that the high-risk patients are enriched in the subset with the most changes, it is not clear if the specific drugs used (Melphalan vs IMID vs proteasome inhibitor) or intervention strategy (Cycled vs continuous/maintenance) and perhaps the response achieved (PR vs CR) influences these events. These observations do highlight two important clinical concepts that need to be considered in the future. First, the meaning of a partial response needs further investigation as this may reflect effective elimination of one subclone but not another. Second, because some patients are not changing or can revert back to a previous subclone we need to consider re-chanllenging patients with previously effective regimens when patients progress. Disclosures: Fonseca: Genzyme: Consultancy; Medtronic: Consultancy; BMS: Consultancy; AMGEN: Consultancy; Otsuka: Consultancy; Celgene: Consultancy, Research Funding; Intellikine: Consultancy; Cylene: Research Funding; Onyx: Research Funding; FISH probes prognostication in myeloma: Patents & Royalties. Stewart:Millennium: Consultancy; Celgene: Honoraria. Bergsagel:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Millennium: Speakers Bureau; Novartis: Speakers Bureau.

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