Evidence map›Paper›PMID 42783770›Full record

ArticleMetabolites2026

Integrated Metabolomic and Proteomic Analyses Reveal Differential Regulation of the Citrate Cycle and Pentose Phosphate Pathway by

Yujin Natori, Dai Mizuno, Masaru Doshi, Masahiro Kawahara, Akira Ishii

Abstract read
In one paragraph

Article in Metabolites, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yujin NatoriDepartment of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya-shi 466-8550, Japan.
Dai MizunoDepartment of Forensic Medicine, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata-shi 990-9585, Japan.ORCID 0000-0002-4301-829X
Masaru DoshiDepartment of Human Physiology and Pathology, Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku 173-8605, Japan.
Masahiro KawaharaResearch Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shin-machi, Nishitokyo-shi 202-8585, Japan.ORCID 0000-0002-3334-4235
Akira IshiiDepartment of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya-shi 466-8550, Japan.ORCID 0000-0001-6574-6055

Funding

Akira Ishii JP23K18387Yujin Natori JP21K17323 and JP23K09762
6 · The paper itself

Abstract

background

methodsCytotoxicity was evaluated using a lactate dehydrogenase assay. Metabolites and proteins were extracted sequentially from single-cell pellets and analyzed using gas chromatography-tandem mass spectrometry and nano-liquid chromatography-quadrupole-Orbitrap mass spectrometry, respectively. Cannabinoids in the exposure medium were quantified using liquid chromatography-tandem mass spectrometry.

resultsThe lowest CS and HU concentrations that were cytotoxic at 24 h and non-cytotoxic at 3 h were 2000 µg/mL and 20 µM, respectively; CS delivered 166 nM THC, 800 nM tetrahydrocannabinolic acid, and 11.3 nM cannabidiol. After 3 h, HU altered both the metabolome and the proteome, whereas CS altered the metabolome with minimal proteome change (8 of 2720 proteins). Six pathways differed, including the citrate cycle and pentose phosphate pathway. Relative to both the control and CS, HU decreased citrate; increased 2-ketoglutarate, fumarate, malate, gluconate, ribose-5-phosphate and ribose; and increased phosphoenolpyruvate carboxykinase 2, isocitrate dehydrogenase 3 subunit α, 2-oxoglutarate dehydrogenase complex component E1, succinate dehydrogenase flavoprotein subunit, malate dehydrogenase 1, 6-phosphogluconolactonase, 6-phosphogluconate dehydrogenase and phosphoglucomutase-1. CS showed the opposite metabolite changes without corresponding enzyme changes.

conclusionsAt a pre-lethal time point, CS and HU produced metabolic changes in opposite directions-broad suppression versus coordinated mobilisation-despite comparable cytotoxicity at 24 h.

Indexed as

Cannabis sativaGT1-7HU210integrated omicsmetabolomicsneuroblastomaproteomicssynthetic cannabinoids

Identifiers

PMID42783770
PMCPMC13609593

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.