Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers

Curtis, Michael J.; Alexander, Stephen P.H.; Cirino, Giuseppe; Docherty, James R.; George, Christopher H.; Giembycz, Mark A.; Hoyer, Daniel; Insel, Paul A.; Izzo, Angelo A.; Ji, Yong; MacEwan, David J.; Sobey, Christopher G.; Stanford, S Clare; Teixeira, Mauro Martins; Wonnacott, Sue; Ahluwalia, Amrita

doi:10.1111/bph.14153

Cited by 1,253 publications

(1,269 citation statements)

References 7 publications

Supporting

Mentioning

1,233

Contrasting

Unclassified

Order By: Relevance

“…Probability values of <0.05 were considered significant. The data and statistical analysis comply with the recommendations on experimental design and analysis in pharmacology (Curtis et al ., 2018). …”

Section: Methodsmentioning

confidence: 99%

Inhibition of protein arginine methyltransferase 3 activity selectively impairs liver X receptor‐driven transcription of hepatic lipogenic genes in vivo

Nahon

Groeneveldt

Geerling

et al. 2018

British J Pharmacology

View full text Add to dashboard Cite

Background and PurposeAgonists for the liver X receptor (LXR) are considered promising therapeutic moieties in cholesterol‐driven diseases by promoting cellular cholesterol efflux pathways. However, current clinical application of these agents is hampered by concomitant LXR‐induced activation of a lipogenic transcriptional network, leading to hepatic steatosis. Recent studies have suggested that protein arginine methyltransferase 3 (PRMT3) may act as a selective co‐activator of LXR activity. Here, we verified the hypothesis that PRMT3 inhibition selectively disrupts the ability of LXR to stimulate lipogenesis while maintaining its capacity to modulate macrophage cholesterol homeostasis.Experimental ApproachA combination of the LXR agonist T0901317 and palm oil was administered to C57BL/6 mice to maximally stimulate LXR and PRMT3 activity. PRMT3 activity was inhibited using the allosteric inhibitor SGC707.Key ResultsTreatment with SGC707 did not negatively influence the T0901317/palm oil‐induced up‐regulation of the cholesterol efflux ATP‐binding cassette transporter genes, ABCA1 and ABCG1, in peritoneal cells. In contrast, SGC707 treatment was associated with a significant decrease in the hepatic expression of the lipogenic gene fatty acid synthase (−64%). A similar trend was observed for stearoyl‐coenzyme A desaturase and acetyl CoA carboxylase expression (−43%; −56%). This obstruction of lipogenic gene transcription coincided with a significant 2.3‐fold decrease in liver triglyceride content as compared with the T0901317 and palm oil‐treated control group.Conclusion and ImplicationsWe showed that inhibition of PRMT3 activity by SGC707 treatment selectively impairs LXR‐driven transcription of hepatic lipogenic genes, while the positive effect of LXR stimulation on macrophage cholesterol efflux pathways is maintained.

show abstract

Section: Methodsmentioning

confidence: 99%

Inhibition of protein arginine methyltransferase 3 activity selectively impairs liver X receptor‐driven transcription of hepatic lipogenic genes in vivo

Nahon

Groeneveldt

Geerling

et al. 2018

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…17,18 3 | RESULTS For in vitro experiments, no statistical method was used to predetermine the sample size.…”

Section: Statistical Analysesmentioning

confidence: 99%

Pharmacological inhibition of STAT3 pathway ameliorates acute liver injury in vivo via inactivation of inflammatory macrophages and hepatic stellate cells

et al. 2020

View full text Add to dashboard Cite

Abbreviations: AEC, 3-amino-9-ethyl carbazole; Arg1, Arginase 1; CCL2/MCP1, chemokine (C-C motif) ligand 2/Macrophage chemotactic protein-1; CCl 4 , carbon tetrachloride; CCR2, chemokine (C-C motif) receptor 2; DAPI, 4',6-diamidino-2-phenylindole; DMSO, Dimethyl sulfoxide; ECM, extracellular matrix; HRP, horseradish peroxidase; HSCs, hepatic stellate cells; IL-1β, Interleukin 1 beta; IL-6, Interleukin 6; MHC II, major histocompatibility complex class II; MRC1, mannose receptor 1; mRNA, messenger RNAs; NaCl, sodium chloride; NASH, non-alcoholic steatohepatitis; NOS2/iNOS, nitric oxide synthase 2; qRT-PCR, quantitative real-time polymerase chain reaction; SDS, sodium dodecyl sulfate; TGFβ, transforming growth factor beta; Tris-HCl, Tris(hydroxymethyl)aminomethane hydrochloride; YM1, Beta-N-acetyl hexosaminidase or Chi3l3, Chitinase-3-like protein 3; α-SMA, alpha smooth muscle actin. AbstractLiver diseases represent a major health problem worldwide, in particular, acute liver injury is associated with high mortality and morbidity. Inflammatory macrophages and hepatic stellate cells (HSCs) are known to be involved in the pathogenesis of acute liver injury. In this study, we have investigated the implication of STAT3 inhibition in acute liver injury/early fibrogenesis. In fibrotic human livers, we found STAT3 mRNA expression was significantly upregulated and correlated with collagen I expression. In vitro, STAT3 signaling pathway was found to be activated in TGFβ-activated HSCs and inflammatory macrophages. STAT3 inhibitor, WP1066 significantly inhibited TGFβ-induced collagen I, vimentin and α-SMA expression, and contractility in human HSCs. In LPS-and IFNγ-induced pro-inflammatory macrophages, WP1066 strongly attenuated nitric-oxide release and expression of major inflammatory markers such as TNF-α, iNOS, CCL2, IL-1β, IL-6, and CCR2. In vivo in CCl 4 -induced acute liver injury mouse model, WP1066 significantly reduced collagen expression, HSCs activation, and intrahepatic inflammation. Finally, in LPSinduced human hepatic 3D spheroid model, WP1066 inhibited LPS-induced fibrotic and inflammatory parameters. In conclusion, our results demonstrate that the therapeutic inhibition of STAT3 pathway using WP1066 targeting HSCs and inflammatory macrophages suggests a potential pharmacological approach for the treatment of acute liver injury. K E Y W O R D Sacute liver injury, hepatic stellate cells, inflammation, macrophages, STAT3 signaling pathway, WP1066 78 | ÖZTÜRK AKCORA eT Al.

show abstract

“…The data and statistical analysis comply with the recommendations on experimental design and analysis in pharmacology (Curtis et al, 2018). Operators for animal experiments and data analysts were not blinded.…”

Section: Methodsmentioning

confidence: 98%

High‐frequency autonomic modulation: a new model for analysis of autonomic cardiac control

Champéroux

Fesler

Judé

et al. 2018

British J Pharmacology

View full text Add to dashboard Cite

Background and PurposeIncrease in high‐frequency beat‐to‐beat heart rate oscillations by torsadogenic hERG blockers appears to be associated with signs of parasympathetic and sympathetic co‐activation which cannot be assessed directly using classic methods of heart rate variability analysis. The present work aimed to find a translational model that would allow this particular state of the autonomic control of heart rate to be assessed.Experimental ApproachHigh‐frequency heart rate and heart period oscillations were analysed within discrete 10 s intervals in a cohort of 200 healthy human subjects. Results were compared to data collected in non‐human primates and beagle dogs during pharmacological challenges and torsadogenic hERG blockers exposure, in 127 genotyped LQT1 patients on/off β‐blocker treatment and in subgroups of smoking and non‐smoking subjects.Key ResultsThree states of autonomic modulation, S1 (parasympathetic predominance) to S3 (reciprocal parasympathetic withdrawal/sympathetic activation), were differentiated to build a new model of heart rate variability referred to as high‐frequency autonomic modulation. The S2 state corresponded to a specific state during which both parasympathetic and sympathetic systems were coexisting or co‐activated. S2 oscillations were proportionally increased by torsadogenic hERG‐blocking drugs, whereas smoking caused an increase in S3 oscillations.Conclusions and ImplicationsThe combined analysis of the magnitude of high‐frequency heart rate and high‐frequency heart period oscillations allows a refined assessment of heart rate autonomic modulation applicable to long‐term ECG recordings and offers new approaches to assessment of the risk of sudden death both in terms of underlying mechanisms and sensitivity.

show abstract

Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers

Cited by 1,253 publications

References 7 publications

Inhibition of protein arginine methyltransferase 3 activity selectively impairs liver X receptor‐driven transcription of hepatic lipogenic genes in vivo

Inhibition of protein arginine methyltransferase 3 activity selectively impairs liver X receptor‐driven transcription of hepatic lipogenic genes in vivo

Pharmacological inhibition of STAT3 pathway ameliorates acute liver injury in vivo via inactivation of inflammatory macrophages and hepatic stellate cells

High‐frequency autonomic modulation: a new model for analysis of autonomic cardiac control

Contact Info

Product

Resources

About