Pharmacology and Toxicology

Germline cis variant determines epigenetic regulation of the anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase (DPYD)

1. Ting Zhang
2. Alisa Ambrodji
3. Huixing Huang
4. Kelly J Bouchonville
5. Amy S Etheridge
6. Remington E Schmidt
7. Brianna M Bembenek
8. Zoey B Temesgen
9. Zhiquan Wang
10. Federico Innocenti
11. Deborah Stroka
12. Robert B Diasio
13. Carlo R Largiadèr
14. Steven M Offer

• Curated by eLife

  eLife assessment

  This manuscript presents valuable findings on the identification of epigenetically mediated control for the recognition of dihydropyrimidine dehydrogenase (DPYD) gene expression that is linked with cancer treatment resistance using 5-fluorouracil. The evidence is compelling, supported by data from patient-derived specimens and direct assessment of 5-fluorouracil sensitivity, which provides confidence in the proposed mechanisms. The model is additionally supported by genome data from a population with high "compromised allele frequency". This work will interest those studying drug resistance in cancer therapy.

Reviewed by eLife

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia

1. Ling Zhou
2. Chengyang Ni
3. Ruixue Liao
4. Xiaoqin Tang
5. Taian Yi
6. Mei Ran
7. Miao Huang
8. Rui Liao
9. Xiaogang Zhou
10. Dalian Qin
11. Long Wang
12. Feihong Huang
13. Xiang Xie
14. Ying Wan
15. Jiesi Luo
16. Yiwei Wang
17. Jianming Wu

• Curated by eLife

  eLife assessment

  This study presents a rather valuable finding that vilazodone can restore the normal platelet level through regulating 5-HT1A receptor. The evidence supporting the claims of the authors is solid, although inclusion of more cell lines and more detailed analysis of the results would have strengthened the study. The work will be of interest to scientists working in the field of thrombocytopenia.

Reviewed by eLife

PSTPIP2 ameliorates aristolochic acid nephropathy by suppressing interleukin-19-mediated neutrophil extracellular trap formation

1. Changlin Du
2. Chuanting Xu
3. Pengcheng Jia
4. Na Cai
5. Zhenming Zhang
6. Wenna Meng
7. Lu Chen
8. Zhongnan Zhou
9. Qi Wang
10. Rui Feng
11. Jun Li
12. Xiaoming Meng
13. Cheng Huang
14. Taotao Ma

• Curated by eLife

  eLife assessment

  This paper is of interest to a broad audience of cell biologists, and researchers who work in cell death and the role of NETosis in the pathogenesis of chronic diseases. This study presents valuable new insights to support NETosis plays an important role in the development of aristolochic acid nephropathy (AAN). A series of compelling experiments using in vivo and in vitro model supported that AAN induced NET formation via IL-19-IL20-beta receptor can induce inflammation and cell death. This new knowledge of the interaction between kidney cells and neutrophils could have clinical implications in the treatment of AAN.

Reviewed by eLife

Assessing drug safety by identifying the axis of arrhythmia in cardiomyocyte electrophysiology

1. Stewart Heitmann
2. Jamie I Vandenberg
3. Adam P Hill

• Curated by eLife

  eLife assessment

  This compelling and novel mathematical method assesses drug pro-arrhythmic cardiotoxicity by examining the electrophysiology of untreated cardiac cells. It will be valuable for future drug safety design.

Reviewed by eLife

Sophocarpine inhibits TRP channels to produce anti-pruritic and analgesic effects in a mouse model of inflammatory itch and pain

1. Hekun Zeng
2. Peiyang Li
3. Dan Zhou
4. Zhe Zhang
5. Alexei Verkhratsky
6. Hong Nie

Reviewed by Arcadia Science

Metabolomic profiling reveals effects of marein on energy metabolism in HepG2 cells

1. Baoping Jiang
2. Liang Le
3. Keping Hu
4. Lijia Xu
5. Peigen Xiao

Reviewed by preLights

Discovery of a new activator of Slack potassium channels with robust efficacy in models of histamine-independent and chronic itch

1. Annika Balzulat
2. W. Felix Zhu
3. Cathrin Flauaus
4. Victor Hernandez-Olmos
5. Jan Heering
6. Sunesh Sethumadhavan
7. Mariam Dubiel
8. Annika Frank
9. Amelie Menge
10. Maureen Hebchen
11. Katharina Metzner
12. Ruirui Lu
13. Robert Lukowski
14. Peter Ruth
15. Stefan Knapp
16. Susanne Müller
17. Dieter Steinhilber
18. Inga Hänelt
19. Holger Stark
20. Ewgenij Proschak
21. Achim Schmidtko

Reviewed by Arcadia Science

Discovery and biological evaluation of a potent small molecule CRM1 inhibitor for its selective ablation of extranodal NK/T cell lymphoma

1. He Liu
2. Meisuo Liu
3. Xibao Tian
4. Haina Wang
5. Jiujiao Gao
6. Hanrui Li
7. Zhehuan Zhao
8. Yu Liu
9. Caigang Liu
10. Xuan Chen
11. Yongliang Yang

• Curated by eLife

  eLife assessment

  This study reports a valuable finding on the discovery and evaluation of a potent small molecule inhibitor for CRM1 that may be important to treat extranodal NK/T cell lympohma (ENKTL). The evidence supporting the claims of the authors is solid that reflects an important finding for novel CRM1 inhibitors to treat ENKTL, although additional experimental evidence is needed. The work will be of interest to cancer biologists working on ENKTL.

Reviewed by eLife

A novel triptolide analog downregulates NF-κB and induces mitochondrial apoptosis pathways in human pancreatic cancer

1. Qiaomu Tian
2. Peng Zhang
3. Yihan Wang
4. Youhui Si
5. Dengping Yin
6. Christopher R Weber
7. Melissa L Fishel
8. Karen E Pollok
9. Bo Qiu
10. Fei Xiao
11. Anita S Chong

• Curated by eLife

  eLife assessment

  This useful manuscript presents a new therapeutic formulation and these solid findings have potential clinical significance as the efficacy of CK21 is relevant in various pancreatic cancer models.Further validation studies would help to strengthen the findings.

Reviewed by eLife

Death by a thousand cuts through kinase inhibitor combinations that maximize selectivity and enable rational multitargeting

1. Ian R Outhwaite
2. Sukrit Singh
3. Benedict-Tilman Berger
4. Stefan Knapp
5. John D Chodera
6. Markus A Seeliger

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on an alternative method that combines multiple inhibitors to maximize on-target inhibition and minimize off-target inhibition. The evidence supporting the claims of the authors is solid, although a proper validation of the methodology could strengthen the paper. The work will be of interest to scientists working in the field of drug discovery, particularly in the field of kinase inhibitors.

Reviewed by eLife