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Record W4284691058 · doi:10.1101/2022.07.06.499010

NAD <sup>+</sup> repletion with niacin counteracts cancer cachexia

2022· preprint· en· W4284691058 on OpenAlexfundno aff
Marc Beltrà, Noora Pöllänen, Claudia Fornelli, Kialiina Tonttila, Myriam Y. Hsu, Sandra Zampieri, Lucia Moletta, Paolo E. Porporato, Riikka Kivelä, Marco Sandri, Juha J. Hulmi, Roberta Sartori, Eija Pirinen, Fabio Penna

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldMedicine
TopicNutrition and Health in Aging
Canadian institutionsnot available
FundersAssociazione Italiana per la Ricerca sul CancroUniversità degli Studi di TorinoFondazione Umberto VeronesiTrent UniversityNottingham Trent University
KeywordsNAD+ kinaseNiacinCachexiaNicotinamide mononucleotideWastingCancerNicotinamide phosphoribosyltransferaseNicotinamide adenine dinucleotideMitochondrionInternal medicineEndocrinologyNicotinamideMedicineBiologyCancer researchBiochemistryEnzyme

Abstract

fetched live from OpenAlex

SUMMARY 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 confirmed that depletion of NAD + and downregulation of Nrk2 , an NAD + biosynthetic enzyme, are common features of different mouse models and cachectic cancer patients. Testing NAD + repletion therapy in cachectic mice revealed that NAD + precursor, vitamin B3 niacin, efficiently corrected tissue NAD + levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia. To examine NAD + metabolism in a clinical setting, we showed that the low expression of NRK2 in cancer patients correlated with metabolic abnormalities underscoring the significance of NAD + in the pathophysiology of human cancer cachexia. Overall, our results propose a novel therapy target, NAD + metabolism, 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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.001

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 head0.026
GPT teacher head0.284
Teacher spread0.259 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations2
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicNutrition and Health in Aging→French-language works237,207→