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Record W4362522244 · doi:10.1038/s41467-023-37595-6

NAD+ repletion with niacin counteracts cancer cachexia

2023· article· en· W4362522244 on OpenAlexfundno aff
Marc Beltrà, Noora Pöllänen, Claudia Fornelli, Kialiina Tonttila, Myriam Y. Hsu, Sandra Zampieri, Lucia Moletta, Samantha Corrà, Paolo E. Porporato, Riikka Kivelä, Carlo Viscomi, Marco Sandri, Juha J. Hulmi, Roberta Sartori, Eija Pirinen, Fabio Penna

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldMedicine
TopicNutrition and Health in Aging
Canadian institutionsnot available
FundersSyöpäsäätiöFondazione Italiana per la Ricerca sul CancroAssociazione Italiana per la Ricerca sul CancroAcademy of FinlandFondazione Umberto VeronesiTrent UniversityNottingham Trent UniversitySuomen Lääketieteen Säätiö
KeywordsNAD+ kinaseCachexiaNiacinNicotinamide mononucleotideWastingNicotinamide phosphoribosyltransferaseCancerMitochondrionNicotinamide adenine dinucleotideCancer researchNicotinamideMedicineEndocrinologyInternal medicineBiologyBiochemistryEnzyme

Abstract

fetched live from OpenAlex

Abstract Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD + ) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD + and downregulation of Nrk2 , an NAD + biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD + repletion therapy in cachectic mice reveals that NAD + precursor, vitamin B3 niacin, efficiently corrects tissue NAD + levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD + in the pathophysiology of human cancer cachexia. Overall, our results propose NAD + metabolism as a therapy target for cachectic cancer patients.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.690
Threshold uncertainty score0.391

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.068
GPT teacher head0.434
Teacher spread0.366 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations71
Published2023
Admission routes1
Has abstractyes

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