scholarly journals Down-regulation of complement genes in lipopolysaccharide-challenged zebrafish (Danio rerio) larvae exposed to Indonesian propolis

2023 ◽  
Vol 83 ◽  
Author(s):  
I. Wibowo ◽  
N. Marlinda ◽  
F. R. Nasution ◽  
R. E. Putra ◽  
N. Utami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Danio Rerio ◽  
Complement System ◽  
Yolk Sac ◽  
Liver Histology ◽  
Histological Structure ◽  
Down Regulation ◽  
Expression Levels ◽  
Zebrafish Larvae ◽  
Complement Gene

Abstract Although propolis has been reported for having anti-inflammatory activities, its effects on complement system has not been much studied. This research was conducted to find out the effects of Indonesian propolis on the expression levels of C3, C1r/s, Bf, MBL, and C6 in zebrafish larvae which were induced by lipopolysaccharide (LPS). Counting of macrophages migrating to yolk sac and liver histology were carried out. Larvae were divided into four groups: CON (cultured in E3 medium only), LPS (cultured in a medium containing 0.5 μg/L LPS), LPSIBU (cultured in a medium containing LPS, and then treated with 100 μg/L ibuprofen for 24 hours), and LPSPRO (cultured in a medium containing LPS, and then immersed in 14,000 μg/L propolis for 24 hours) groups. The results showed that complement gene expression in larvae from the LPSIBU and LPSPRO groups were generally lower than in larvae from the LPS group. The number of macrophage migrations to the yolk in the LPSPRO group was also lower than in the LPS group. Histological structure of liver in all groups were considered normal. This study shows that Indonesian propolis has the potential to be used as an alternative to the substitution of NSAIDs.

scholarly journals Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: a transcriptomic study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Amer Toutonji ◽  
Mamatha Mandava ◽  
Silvia Guglietta ◽  
Stephen Tomlinson
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Complement System ◽  
Classical Pathway ◽  
Post Injury ◽  
Complement Inhibition ◽  
Time Points ◽  
Complement Gene ◽  
The Complement System

AbstractActivation of the complement system propagates neuroinflammation and brain damage early and chronically after traumatic brain injury (TBI). The complement system is complex and comprises more than 50 components, many of which remain to be characterized in the normal and injured brain. Moreover, complement therapeutic studies have focused on a limited number of histopathological outcomes, which while informative, do not assess the effect of complement inhibition on neuroprotection and inflammation in a comprehensive manner. Using high throughput gene expression technology (NanoString), we simultaneously analyzed complement gene expression profiles with other neuroinflammatory pathway genes at different time points after TBI. We additionally assessed the effects of complement inhibition on neuropathological processes. Analyses of neuroinflammatory genes were performed at days 3, 7, and 28 post injury in male C57BL/6 mice following a controlled cortical impact injury. We also characterized the expression of 59 complement genes at similar time points, and also at 1- and 2-years post injury. Overall, TBI upregulated the expression of markers of astrogliosis, immune cell activation, and cellular stress, and downregulated the expression of neuronal and synaptic markers from day 3 through 28 post injury. Moreover, TBI upregulated gene expression across most complement activation and effector pathways, with an early emphasis on classical pathway genes and with continued upregulation of C2, C3 and C4 expression 2 years post injury. Treatment using the targeted complement inhibitor, CR2-Crry, significantly ameliorated TBI-induced transcriptomic changes at all time points. Nevertheless, some immune and synaptic genes remained dysregulated with CR2-Crry treatment, suggesting adjuvant anti-inflammatory and neurotropic therapy may confer additional neuroprotection. In addition to characterizing complement gene expression in the normal and aging brain, our results demonstrate broad and chronic dysregulation of the complement system after TBI, and strengthen the view that the complement system is an attractive target for TBI therapy.

scholarly journals High-throughput mRNA sequencing of stromal cells from endometriomas and endometrium

Reproduction ◽  
2017 ◽  
Vol 154 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Kadri Rekker ◽  
Merli Saare ◽  
Elo Eriste ◽  
Tõnis Tasa ◽  
Viktorija Kukuškina ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Throughput ◽  
Complement System ◽  
Stromal Cells ◽  
Cell Types ◽  
Coagulation Cascade ◽  
Expression Levels ◽  
Mrna Sequencing ◽  
Standard Design ◽  
Gene Expression Levels

The aetiology of endometriosis is still unclear and to find mechanisms behind the disease development, it is important to study each cell type from endometrium and ectopic lesions independently. The objective of this study was to uncover complete mRNA profiles in uncultured stromal cells from paired samples of endometriomas and eutopic endometrium. High-throughput mRNA sequencing revealed over 1300 dysregulated genes in stromal cells from ectopic lesions, including several novel genes in the context of endometriosis. Functional annotation analysis of differentially expressed genes highlighted pathways related to cell adhesion, extracellular matrix–receptor interaction and complement and coagulation cascade. Most importantly, we found a simultaneous upregulation of complement system components and inhibitors, indicating major imbalances in complement regulation in ectopic stromal cells. We also performed in vitro experiments to evaluate the effect of endometriosis patients’ peritoneal fluid (PF) on complement system gene expression levels, but no significant impact of PF on C3, CD55 and CFH levels was observed. In conclusion, the use of isolated stromal cells enables to determine gene expression levels without the background interference of other cell types. In the future, a new standard design studying all cell types from endometriotic lesions separately should be applied to reveal novel mechanisms behind endometriosis pathogenesis.

scholarly journals Exploration of Stereoselectivity in Embryo-Larvae (Danio rerio) Induced by Chiral PCB149 at the Bioconcentration and Gene Expression Levels

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0155263 ◽  
Author(s):  
Tingting Chai ◽  
Feng Cui ◽  
Xiyan Mu ◽  
Yang Yang ◽  
Chengju Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Danio Rerio ◽  
Expression Levels ◽  
Gene Expression Levels

scholarly journals Effectiveness of hCMV, mEF1a and mAct promoters on driving of foreign gene expression in transgenic zebrafish

2007 ◽  
Vol 6 (1) ◽  
pp. 65
Author(s):  
. Alimuddin ◽  
G. Yoshizaki ◽  
O. Carman ◽  
T. Takeuchi
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Danio Rerio ◽  
Elongation Factor ◽  
Masu Salmon ◽  
Transgenic Zebrafish ◽  
Foreign Gene ◽  
Oncorhynchus Masou ◽  
Expression Levels ◽  
F2 Generation

<p>Highly unsaturated fatty acids (HUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have long been recognized for its beneficial effect for human health and development.   The D6 fatty acid desaturase is generally considered to be the rate-limiting factor in HUFA biosynthesis.  Here, as the first step of study, we conducted experiment to select an appropriate construct that allows higher expression levels of masu salmon (<em>Oncorhynchus masou</em>)<em> </em>D6-desaturase gene in zebrafish (<em>Danio rerio</em>) in order to increase its activity for synthesizing EPA/DHA.  Salmon D6-desaturase cDNA (sD6) was separately ligated with human cytomegalovirus (hCMV), medaka elongation factor 1a (mEF1a) and medaka b-actin (mAct) promoters.  The resulted construct was designated as hCMV-sD6, mEF1a-sD6 and mAct-sD6, respectively.  Each of the constructs in circular DNA form was microinjected into 1-cell stage embryos at a concentration of 30mg/ml. Transgenic individuals were identified by polymerase chain reaction (PCR) and their expression levels were analyzed by reverse transcription PCR.  The first (F1) and second (F2) generation was produced by crossing the transgenic founder F0 and F1, respectively, with wild-type fish.  The results showed that the highest transient gene expression level was obtained from the mAct-D6 construct, followed respectively by EF1a-D6 and hCMV-D6 construct. The transmission rate of transgene into F1 generation was 4.2%-44.1%, and into F2 was followed the Mendellian segregation pattern.   Expression of transgene in F2 generation was varied between strains regarding as the mosaics of F0 fish.  Now, a transgenic system to study the modification of fatty acid biosynthesis pathways in fish was established.  Further investigations are to produce fish containing higher levels of EPA and DHA.</p> <p>Keywords: desaturase, nutraceutical fatty acid, transgenic, zebrafish, masu salmon</p> <p> </p> <p>Abstrak</p> <p>Promoter merupakan regulator yang menentukan tempat, waktu dan tingkat ekspresi gen.  Pada penelitian ini, kami melakukan seleksi kontruksi plasmid yang tepat yang menghasilkan tingkat ekspresi yang tinggi dari gen D6-desaturase-like ikan masu salmon (<em>Oncorhynchus masou</em>)<em> </em>yang ditransfer ke ikan zebra (<em>Danio rerio</em>) untuk meningkatkan kemampuannya dalam mensintesa EPA/DHA.  cDNA D6-desaturase-like (OmD6FAD) dari ikan salmon masu diligasi secara terpisah dengan promoter dari cytomegalovirus manusia (hCMV), elongation factor 1a (mEF1a) dan b-actin (mbAct) dari ikan medaka, untuk membuat konstruksi plasmid yang berturut-turut disebut sebagai hCMV-OmD6FAD, mEF1a- OmD6FAD dan mbAct-OmD6FAD. Konstruksi tersebut dengan konsentrasi 30mg/ml disuntikkan ke embrio pada saat fase satu sel. Individu transgenik diidentifikasi menggunakan PCR dan tingkat ekspresi transgen dianalisa dengan RT-PCR.   Hasil menunjukkan bahwa tingkat ekspresi sementara yang tertinggi dari gen asing adalah diperoleh dari konstruksi mbAct-OmD6FAD, diikuti selanjutnya oleh EF1a-OmD6FAD dan hCMV- OmD6FAD. Transgen telah ditransmisikan ke ikan generasi F2 dengan mengikuti pola segregasi Mendel. Tingkat ekspresi transgen yang tinggi pada jaringan ikan F2 yang diperiksa telah diperoleh.  Dengan demikian, sebuah sistem transgenik untuk memodifikasi biosistesa asam lemak pada ikan telah dikembangkan. </p> <p>Kata kunci: promoter, desaturase asam lemak, transgenik, ikan zebra, ikan salmon masu</p>

Aberrant Gene Expression of BAALC and ERG in Older [≥60 Years (y)] De Novo Cytogenetically Normal Acute Myeloid Leukemia (CN-AML): A Cancer and Leukemia Group B (CALGB) Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 214-214
Author(s):  
Sebastian Schwind ◽  
Guido Marcucci ◽  
Kati Maharry ◽  
Krzysztof Mrózek ◽  
Michael D. Radmacher ◽  
...  
Keyword(s):  
Gene Expression ◽  
Internal Control ◽  
Hox Genes ◽  
Conflicts Of Interest ◽  
Age Groups ◽  
Prognostic Impact ◽  
Stem Cell Markers ◽  
Down Regulation ◽  
Expression Levels ◽  
Lower Expression

Abstract Abstract 214 BAALC & ERG are aberrantly expressed in younger (<60 y) adult CN-AML patients (pts), where expression levels of these genes are also associated with clinical outcome. Whether aberrant BAALC & ERG expression also occurs in older (≥60 y) CN-AML pts is unknown. To assess the BAALC & ERG expression levels in older CN-AML & their impact on outcome we studied pts ≥60 y (median age, 68 y; range 60–83) enrolled on cytarabine/daunorubicin-based protocols [CALGB 10201, 9720, 9420, 8923, 8525], with diagnostic blood samples available for quantitative RT-PCR analysis (n=158), that were also characterized for other molecular prognosticators (FLT3-ITD, FLT3-TKD, NPM1 & WT1 mutations). BAALC & ERG expression values were normalized to an internal control (ABL1), & the median gene expression value was used to define high & low expressers for BAALC & ERG. Gene (GEP) & microRNA (MEP) expression profiling were done using, respectively, Affymetrix U133 plus 2.0 & OSU CCC v4.0 arrays. At diagnosis, lower BAALC expression was associated with mutated NPM1 (P<.001) & low ERG expression (P<.001). Lower BAALC expressers had a higher complete remission rate (CR; 86% v 54%, P<.001) & longer disease-free (DFS; P=.006; 3y rates 19% v 12%) & overall survival (OS; P<.001; 3y 29% v 10%) than higher expressers. Lower ERG expression was associated with lower WBC (P=.005), % marrow (BM; P=.001) & blood (P<.001) blasts & absent FLT3-ITD (P<.001) & low BAALC expression (P<.001). Lower ERG expression also associated with longer DFS (P=.001; 3y 18% v 14%) & OS (P<.001; 3y 24% v 15%). In multivariable models (Table 1), low BAALC expression independently associated with CR & longer DFS. BAALC & ERG expression were the only factors associated with OS. Comparison of age-groups (60-69 y v ≥70 y; Table 2) showed BAALC expression had a stronger prognostic impact in ≥70 y pts; lower expression was associated with higher CR rates & longer DFS & OS. ERG expression had instead stronger prognostic impact in 60-69 y pts (Table 2); lower expression was associated with longer DFS & OS. GEP (482 probes) & MEP (22 probes) differentiated low from high BAALC expressers. Low BAALC expressers had down-regulation of stem cell markers (CD34, CD133) & unfavorable outcome predictors (HGF, MN1, CD200), & up-regulation of HOX genes & miR-10a & miR-10b. GEP (1554 probes) & MEP (11 probes) differentiating low from high ERG expressers showed low ERG expressers had down-regulation of DNMT3B & up-regulation of topoisomerase 1 (TOP1), which is associated with enhanced chemotherapy sensitivity. Among up-regulated microRNAs in low ERG expressers was miR-208a, which is predicted to target ERG. In conclusion, lower expression of both BAALC & ERG associated with better outcome in older CN-AML pts even in the context of other established prognostic molecular markers, but have different impact on age-groups. GEP & MEP provided novel information that may elucidate how differential expression levels of these genes contribute to leukemogenesis & aid in developing novel risk-adapted therapies. Disclosures: No relevant conflicts of interest to declare.

Identification of predictive and surrogate molecular markers for dasatinib in prostate cancer: Rationale for patient selection and efficacy monitoring

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3579-3579
Author(s):  
X. Wang ◽  
K. Reeves ◽  
R. Luo ◽  
S. Wu ◽  
L. Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Molecular Markers ◽  
Cell Lines ◽  
Myelogenous Leukemia ◽  
Published Data ◽  
Down Regulation ◽  
Data Set ◽  
Expression Levels ◽  
Dasatinib Treatment

3579 Background: Dasatinib is a potent, multi-targeted kinase inhibitor that was recently approved for treatment of chronic myelogenous leukemia resistant to imatinib. To aid its clinical development in prostate cancer, we used a panel of prostate cancer cell lines to identify molecular markers that could be used to predict sensitivity to dasatinib and to monitor its activity. Methods: Baseline gene expression profiles of 16 cell lines were used to identify predictive biomarkers based on the correlation of gene expression with in vitro sensitivity of cells to dasatinib. Selected cell lines were treated with dasatinib to identify surrogate biomarkers based upon changes in gene expression following dasatinib treatment. Results: We identified 174 genes whose baseline expression levels were highly correlated with sensitivity or resistance to dasatinib. These include cell lineage markers cytokeratin 5 (CK5), androgen receptor (AR), and prostate specific antigen (PSA). Our results indicate that “basal type” cell lines (those with high expression of CK5 and low expression of AR and PSA) are sensitive to dasatinib. Dasatinib treatment studies further identified genes whose expression levels were significantly modulated by the drug. Ten genes, including urokinase-type plasminogen activator (uPA), were not only significantly correlated with sensitivity to dasatinib but also reduced in their expression upon drug treatment. In addition, the down-regulation of uPA was specific to dasatinib and the effect was not seen in taxol-treated cells. The extent of down-regulation was correlated with the sensitivity of cell lines to dasatinib. EphA2, a specific kinase target of dasatinib, was identified as a biomarker common to prostate and breast cancers. Finally, the expression of 5 genes including CK5, AR, PSA, uPA and EphA2 in prostate tumors was examined and the dasatinib sensitivity signature was validated using a published data set derived from a clinical population. Conclusions: Candidate markers correlated with dasatinib sensitivity were identified. A five-gene model consisting of predictive markers as well as potential surrogate markers has been formulated and will be evaluated in ongoing dasatinib prostate cancer trials. No significant financial relationships to disclose.

scholarly journals Diet Effects on Growth, Mortality, RNA: DNA Ratio and Gene Expression of Zebrafish Danio rerio

2020 ◽  
Vol 4 (1) ◽  
pp. 19-27
Author(s):  
Md. Golam Rabbane ◽  
Md. Yousuf Ali ◽  
Md. Al Zahid ◽  
Jakir Hossain
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Weight Gain ◽  
Growth Performance ◽  
Molecular Analysis ◽  
Danio Rerio ◽  
Significant Contribution ◽  
Egg Yolk ◽  
Down Regulation ◽  
Length Gain

This study evaluated the effects of different combination of commercial and natural diets (T1: egg yolk, T2: egg yolk+ Artemia, T3: Horlicks, T4: Horlicks+ Artemia, T5: TetraBits, T6: TetraBits+ Artemia, T7: NovoTom, T8: NovoTom+ Artemia) on growth, mortality, RNA: DNA ratio and gene expression of zebrafish for a period of 45 days. Significantly highest length (2.75±0.04 cm) and weight (0.25±0.10 g) gain were recorded in T2 treatment. Lowest length gain (2.00±0.08 cm) and weight gain (0.14±0.12 g) were calculated in T3. Significant highest mortality (65.00±8.66%) was observed in treatment T7 followed by T5 and T8 and significant lowest mortality (20.00±7.64%) was recorded in T2. By molecular analysis, Highest RNA: DNA ratio was found (1.01) in T5 followed by T4 (0.95) and lowest was found in T1 (0.77). Interestingly, a similar result was observed for gh1 (Growth hormone 1) gene expression. Highest gene expression was found in T5 followed by T4 and lowest in T2. Significant down regulation was observed in T2 for gh1 gene. Finally, the study would suggest that zebrafish can be fed with egg yolk+Artemia for better growth performance. The findings could provide a significant contribution to the field of global zebrafish as well as aquaculture research.

scholarly journals The effect of rotenone on synuclein and neurotrophic factor gene expression levels in zebrafish larvae

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S103
Author(s):  
Anwar Norazit ◽  
Sharvin Manickam ◽  
Agnes Ong Lee Chen ◽  
David Wong Chee Earn ◽  
Suzita Mohd Noor
Keyword(s):  
Gene Expression ◽  
Neurotrophic Factor ◽  
Factor Gene ◽  
Expression Levels ◽  
Zebrafish Larvae ◽  
Gene Expression Levels
Sign in / Sign up

Export Citation Format

Share Document