Pharmacology and Toxicology

Target protein identification in live cells and organisms with a non-diffusive proximity tagging system

1. Yingjie Sun
2. Changheng Li
3. Xiaofei Deng
4. Wenjie Li
5. Xiaoyi Deng
6. Weiqi Ge
7. Miaoyuan Shi
8. Ying Guo
9. Yanxun V Yu
10. Hai-Bing Zhou
11. Youngnam N Jin

• Curated by eLife

  eLife Assessment

  The study presents important findings that reveal SEPHS2 and VPS37C as new potential drug targets for dasatinib and hydroxychloroquine respectively in addition to confirming known targets of these drugs. The evidence provided is solid, however, some of the claims are not fully supported by the data. To enhance the conclusions and readability, the writing clarity, data analysis and justification of experimental design rationale need to be worked on to enhance the study's interest among chemical biologists, biochemists, and scientists in drug discovery.

Reviewed by eLife

Visualization of endogenous G proteins on endosomes and other organelles

1. Wonjo Jang
2. Kanishka Senarath
3. Gavin Feinberg
4. Sumin Lu
5. Nevin A Lambert

• Curated by eLife

  eLife assessment

  This important study investigates the intracellular localization patterns of G proteins involved in GPCR signaling, presenting compelling evidence for their preference for plasma and lysosomal membranes over endosomal, endoplasmic reticulum, and Golgi membranes. This discovery has significant implications for understanding GPCR action and signaling from intracellular locations. This research will interest cell biologists studying protein trafficking and pharmacologists exploring localized signaling phenomena.

Reviewed by eLife

SntB triggers the antioxidant pathways to regulate development and aflatoxin biosynthesis in Aspergillus flavus

1. Dandan Wu
2. Chi Yang
3. Yanfang Yao
4. Dongmei Ma
5. Hong Lin
6. Ling Hao
7. Wenwen Xin
8. Kangfu Ye
9. Minghui Sun
10. Yule Hu
11. Yanling Yang
12. Zhenhong Zhuang

• Curated by eLife

  eLife assessment

  In this useful study, the authors investigate the regulatory mechanisms related to toxin production and pathogenicity in Aspergillus flavus. Their observations indicate that the SntB protein regulates morphogenesis, aflatoxin biosynthesis, and the oxidative stress response. The data supporting the conclusions are compelling and contribute significantly the advancing the understanding of SntB function.

Reviewed by eLife

Synthesis and Biological Assessment of Chalcone and Pyrazoline Derivatives as Novel Inhibitor for ELF3-MED23 Interaction

1. Soo-Yeon Hwang
2. Kyung-Hwa Jeon
3. Hwa-Jong Lee
4. Inhye Moon
5. Sehyun Jung
6. Seul-Ah Kim
7. Hyunji Jo
8. Seojeong Park
9. Misun Ahn
10. Soo-Yeon Kwak
11. Younghwa Na
12. Youngjoo Kwon

• Curated by eLife

  eLife assessment

  This valuable study characterized a new set of small molecules targeting the interaction between ELF3-MED23, with one of the reported compounds representing a promising novel therapeutic strategy, The evidence supporting the conclusions is convincing. This article will be of interest to medical and cell biologists working on cancer and, particularly, on HER2-overexpression cancers.

Reviewed by eLife

Noncaloric monosaccharides induce excessive sprouting angiogenesis in zebrafish via foxo1a-marcksl1a signal

1. Xiaoning Wang
2. Jinxiang Zhao
3. Jiehuan Xu
4. Bowen Li
5. Xia Liu
6. Gangcai Xie
7. Xuchu Duan
8. Dong Liu

• Curated by eLife

  eLife assessment

  This valuable study investigates the effect of noncaloric monosaccharides, sugar substitutes that are commonly used by diabetic patients, on angiogenesis in the zebrafish embryo. The authors show that noncaloric monosaccharides and glucose similarly induce excessive blood vessel formation due to the increased formation of tip cells by endothelial cells through the foxo1a-marcksl1a pathway. This solid study is of interest for the medical community in charge of the prevention and of the treatment of diabetes and other metabolic diseases.

Reviewed by eLife

Trazodone, dibenzoylmethane and tauroursodeoxycholic acid do not prevent motor dysfunction and neurodegeneration in Marinesco-Sjögren syndrome mice

1. Giada Lavigna
2. Anna Grasso
3. Chiara Pasini
4. Valentina Grande
5. Laura Mignogna
6. Elena Restelli
7. Antonio Masone
8. Claudia Fracasso
9. Jacopo Lucchetti
10. Marco Gobbi
11. Roberto Chiesa

Reviewed by Review Commons

Nonspecific membrane bilayer perturbations by ivermectin underlie SARS-CoV-2 in vitro activity

1. Richard T Eastman
2. Radda Rusinova
3. Karl F Herold
4. Xi-Ping Huang
5. Patricia Dranchak
6. Ty C Voss
7. Sandeep Rana
8. Jonathan H Shrimp
9. Alex D White
10. Hugh C Hemmings
11. Bryan L Roth
12. James Inglese
13. Olaf S Andersen
14. Jayme L Dahlin

Reviewed by Rapid Reviews Infectious Diseases

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