Human mechanistic target of rapamycin kinase / MTOR

evidence_access

Primary abstract

experimental_model

Human osteoblast-like cell study.

limitations

No direct binding target or dietary requirement is established.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A growth-related pathway accompanied matrix production.

primary_references

Orthosilicic Acid Accelerates Bone Formation in Human Osteoblast-Like Cells Through the PI3K-Akt-mTOR Pathway. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30421162/ · DOI 10.1007/s12011-018-1574-9

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 168–174

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human osteoblast-like cell study. · source_derived_draft · unverified_draft

## silica-pi3k-mtor A growth-related pathway accompanied matrix production. Orthosilicic acid increased PI3K, phosphorylated Akt and mTOR together with osteogenic markers. Model: Human osteoblast-like cell study. Limitations: No direct binding target or dietary requirement is established. Evidence access: Primary abstract Orthosilicic Acid Accelerates Bone Formation in Human Osteoblast-Like Cells Through the PI3K-Akt-mTOR Pathway. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30421162/ · DOI 10.1007/s12011-018-1574-9

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text, Figure 2

experimental_model

Human HeLa cells, depleted media and amino-acid add-back.

limitations

S6K phosphorylation is a pathway readout, not direct tryptophan binding to MTOR.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

Local depletion reduced a growth signal as well as changing metabolite supply.

primary_references

IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23264892/ · DOI 10.4161/onci.21716

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 402–408

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HeLa cells, depleted media and amino-acid add-back. · source_derived_draft · unverified_draft

## tryptophan-trp-mtor Local depletion reduced a growth signal as well as changing metabolite supply. IFN-gamma/IDO-driven tryptophan depletion reduced S6K phosphorylation in human HeLa cells; tryptophan repletion restored the mTOR readout. Model: Human HeLa cells, depleted media and amino-acid add-back. Limitations: S6K phosphorylation is a pathway readout, not direct tryptophan binding to MTOR. Evidence access: Primary full text, Figure 2 IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23264892/ · DOI 10.4161/onci.21716

evidence_access

Primary abstract

experimental_model

Human melanoma models plus cell-free kinase assays.

limitations

Docking was supplemented by biochemical assays; clinical target engagement remains unproven.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

A binding assay supports a more direct target relationship.

primary_references

Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modeling. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24675012/ · DOI 10.1016/j.bcp.2014.03.007

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 272–278

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human melanoma models plus cell-free kinase assays. · source_derived_draft · unverified_draft

## fisetin-mtor-binding A binding assay supports a more direct target relationship. Cell-free competition and activity assays supported fisetin binding and inhibition of mTOR in the human melanoma study. Model: Human melanoma models plus cell-free kinase assays. Limitations: Docking was supplemented by biochemical assays; clinical target engagement remains unproven. Evidence access: Primary abstract Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modeling. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24675012/ · DOI 10.1016/j.bcp.2014.03.007

experimental_model

Biochemical kinase assays plus MDA-MB-231 and A549 cell experiments.

limitations

PI3K isoform is not assigned from abstract; docking is a model, not a solved ligand structure.

nutrient_topic

EGCG collection; comparator and shared-pathway records retain their actual intervention. · Epigallocatechin-3-gallate (EGCG)

plain_language

EGCG competed with the enzyme’s energy substrate.

primary_references

Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21300025/ · DOI 10.1016/j.bbrc.2011.02.010

EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 220–226

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Biochemical kinase assays plus MDA-MB-231 and A549 cell experiments. · source_derived_draft · unverified_draft

## egcg-mtor EGCG competed with the enzyme’s energy substrate. EGCG showed ATP-competitive inhibition with Ki 320 nanomolar in the reported enzyme assay. Model: Biochemical kinase assays plus MDA-MB-231 and A549 cell experiments. Limitations: PI3K isoform is not assigned from abstract; docking is a model, not a solved ligand structure. Evidence access: primary abstract. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21300025/ · DOI 10.1016/j.bbrc.2011.02.010

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation

exposure

Defined biotin deficiency and signaling experiments

limitations

Cell-culture inflammation does not show that extra biotin treats autoimmune disease in replete people.

nutrient_topic

Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin

organism

Homo sapiens

plain_language

Activated T cells released more of one inflammatory signal.

primary_references

[b7-p29531163] Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29531163/ DOI: 10.4049/jimmunol.1701200

tissue_or_cell_type

Activated CD4 T cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 1053–1064

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation · source_derived_draft · unverified_draft

### b7-immune-ifng Biotin-deficient human CD4 T cells secreted more IFN-gamma after anti-CD3/CD28 stimulation. Condition category: nutrient_deficiency nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated T cells released more of one inflammatory signal. organism: Homo sapiens tissue_or_cell_type: Activated CD4 T cells experimental_model: Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation limitations: Cell-culture inflammation does not show that extra biotin treats autoimmune disease in replete people. exposure: Defined biotin deficiency and signaling experiments evidence_span: {"source_cache": "artifacts/biotin-research/29531163.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f", "start_char": 0, "end_char": 1720, "text_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f"} [b7-p29531163] Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29531163/ DOI: 10.4049/jimmunol.1701200

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation

exposure

Defined biotin deficiency and signaling experiments

limitations

Cell-culture inflammation does not show that extra biotin treats autoimmune disease in replete people.

nutrient_topic

Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin

organism

Homo sapiens

plain_language

The response also shifted toward an IL-17-associated inflammatory pattern.

primary_references

[b7-p29531163] Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29531163/ DOI: 10.4049/jimmunol.1701200

tissue_or_cell_type

Activated CD4 T cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 1079–1090

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation · source_derived_draft · unverified_draft

### b7-immune-il17 Biotin-deficient human CD4 T cells secreted more IL-17 after anti-CD3/CD28 stimulation. Condition category: nutrient_deficiency nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response also shifted toward an IL-17-associated inflammatory pattern. organism: Homo sapiens tissue_or_cell_type: Activated CD4 T cells experimental_model: Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation limitations: Cell-culture inflammation does not show that extra biotin treats autoimmune disease in replete people. exposure: Defined biotin deficiency and signaling experiments evidence_span: {"source_cache": "artifacts/biotin-research/29531163.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f", "start_char": 0, "end_char": 1720, "text_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f"} [b7-p29531163] Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29531163/ DOI: 10.4049/jimmunol.1701200

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/29531163.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f", "start_char": 0, "end_char": 1720, "text_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f"}

experimental_model

Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation

exposure

Defined biotin deficiency and signaling experiments

limitations

Cell-culture inflammation does not show that extra biotin treats autoimmune disease in replete people.

nutrient_topic

Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin

organism

Homo sapiens

plain_language

Changes in metabolic signaling accompanied the altered immune response.

primary_references

[b7-p29531163] Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29531163/ DOI: 10.4049/jimmunol.1701200

tissue_or_cell_type

Activated CD4 T cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 1092–1103

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation · source_derived_draft · unverified_draft

### b7-immune-mtor The study linked the heightened inflammatory response of biotin-deficient human CD4 T cells to enhanced mTOR-pathway activation. Condition category: nutrient_deficiency nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changes in metabolic signaling accompanied the altered immune response. organism: Homo sapiens tissue_or_cell_type: Activated CD4 T cells experimental_model: Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation limitations: Cell-culture inflammation does not show that extra biotin treats autoimmune disease in replete people. exposure: Defined biotin deficiency and signaling experiments evidence_span: {"source_cache": "artifacts/biotin-research/29531163.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f", "start_char": 0, "end_char": 1720, "text_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f"} [b7-p29531163] Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29531163/ DOI: 10.4049/jimmunol.1701200

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation

exposure

Defined biotin deficiency and signaling experiments

limitations

Cell-culture inflammation does not show that extra biotin treats autoimmune disease in replete people.

nutrient_topic

Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin

organism

Homo sapiens

plain_language

A second inflammatory signal also increased.

primary_references

[b7-p29531163] Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29531163/ DOI: 10.4049/jimmunol.1701200

tissue_or_cell_type

Activated CD4 T cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 1066–1077

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation · source_derived_draft · unverified_draft

### b7-immune-tnf Biotin-deficient human CD4 T cells secreted more TNF after anti-CD3/CD28 stimulation. Condition category: nutrient_deficiency nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second inflammatory signal also increased. organism: Homo sapiens tissue_or_cell_type: Activated CD4 T cells experimental_model: Anti-CD3/CD28-stimulated human CD4 T cells in biotin-deficient culture; separate mouse validation limitations: Cell-culture inflammation does not show that extra biotin treats autoimmune disease in replete people. exposure: Defined biotin deficiency and signaling experiments evidence_span: {"source_cache": "artifacts/biotin-research/29531163.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f", "start_char": 0, "end_char": 1720, "text_sha256": "64511b88fc7991ad24a1d7c122f5147b1bd99522532fa61752b439f39d363b6f"} [b7-p29531163] Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29531163/ DOI: 10.4049/jimmunol.1701200

evidence_span

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experimental_model

Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate

exposure

Training of myeloid cells with statins to block mevalonate generation, and monocytes from mevalonate kinase deficient patients

limitations

The patient arm is a natural experiment in the opposite direction, which is what makes the mevalonate assignment convincing. The statin result is inhibition of an induced laboratory response.

nutrient_topic

Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

organism

Human

plain_language

It is the intermediate and not the cholesterol that does the training, and people who cannot clear that intermediate are permanently trained.

primary_references

[bg-p29328908] Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29328908/ DOI: 10.1016/j.cell.2017.11.025

tissue_or_cell_type

Monocyte

Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 463–474

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate · source_derived_draft · unverified_draft

### bg-mevalonate-not-cholesterol-trains Activation of the cholesterol synthesis pathway but not the synthesis of cholesterol itself is essential for training of myeloid cells, rather the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways, statins which block mevalonate generation prevent trained immunity induction, and monocytes of patients with hyper immunoglobulin D syndrome who are mevalonate kinase deficient and accumulate mevalonate have a constitutive trained immunity phenotype at both immunological and epigenetic levels. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: It is the intermediate and not the cholesterol that does the training, and people who cannot clear that intermediate are permanently trained. organism: Human tissue_or_cell_type: Monocyte experimental_model: Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate limitations: The patient arm is a natural experiment in the opposite direction, which is what makes the mevalonate assignment convincing. The statin result is inhibition of an induced laboratory response. exposure: Training of myeloid cells with statins to block mevalonate generation, and monocytes from mevalonate kinase deficient patients evidence_span: {"source_cache": "artifacts/glucan-research/29328908.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03", "start_char": 0, "end_char": 1173, "text_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03"} [bg-p29328908] Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29328908/ DOI: 10.1016/j.cell.2017.11.025

evidence_span

{"source_cache": "artifacts/glucan-research/25258083.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872", "start_char": 0, "end_char": 1225, "text_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872"}

experimental_model

Histone modification profiling and genome-wide transcriptome of trained human monocytes, with pathway inhibition and a myeloid conditional knockout

exposure

Beta-glucan training with inhibition of Akt, mTOR or HIF-1 alpha, and metformin as an AMPK activator

limitations

The metformin result is an experimental inhibition of an induced response, not a clinical interaction study.

nutrient_topic

Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

organism

Human cells and mouse

plain_language

The rewiring costs energy: block the cell from burning glucose the fast way and the training does not take.

primary_references

[bg-p25258083] mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. (2014). https://pubmed.ncbi.nlm.nih.gov/25258083/ DOI: 10.1126/science.1250684

tissue_or_cell_type

Monocyte

Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 437–448

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Histone modification profiling and genome-wide transcriptome of trained human monocytes, with pathway inhibition and a myeloid conditional knockout · source_derived_draft · unverified_draft

### bg-training-needs-aerobic-glycolysis Trained monocytes display high glucose consumption, high lactate production and a high ratio of NAD+ to NADH, reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin through a dectin-1-Akt-HIF-1 alpha pathway, inhibition of Akt, mTOR or HIF-1 alpha blocked monocyte induction of trained immunity whereas the AMP-activated protein kinase activator metformin inhibited the innate immune response to fungal infection, and mice with a myeloid cell-specific defect in HIF-1 alpha were unable to mount trained immunity against bacterial sepsis. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: The rewiring costs energy: block the cell from burning glucose the fast way and the training does not take. organism: Human cells and mouse tissue_or_cell_type: Monocyte experimental_model: Histone modification profiling and genome-wide transcriptome of trained human monocytes, with pathway inhibition and a myeloid conditional knockout limitations: The metformin result is an experimental inhibition of an induced response, not a clinical interaction study. exposure: Beta-glucan training with inhibition of Akt, mTOR or HIF-1 alpha, and metformin as an AMPK activator evidence_span: {"source_cache": "artifacts/glucan-research/25258083.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872", "start_char": 0, "end_char": 1225, "text_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872"} [bg-p25258083] mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. (2014). https://pubmed.ncbi.nlm.nih.gov/25258083/ DOI: 10.1126/science.1250684

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human osteoblast-like cultures.

limitations

LY294002 has off-target effects and is not an inhibitor specific to the entire PI3K–Akt–mTOR chain.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

The cell response was sensitive to PI3K-pathway blockade.

primary_references

Orthosilicic Acid Accelerates Bone Formation in Human Osteoblast-Like Cells Through the PI3K-Akt-mTOR Pathway. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30421162/ · DOI 10.1007/s12011-018-1574-9

trigger_kind

machinery_impairment Imported condition classification; unverified.

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 176–182

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human osteoblast-like cultures. · source_derived_draft · unverified_draft

## silica-ly294002-block The cell response was sensitive to PI3K-pathway blockade. LY294002 reduced pathway signals and osteogenic markers during orthosilicic acid treatment. Model: Human osteoblast-like cultures. Limitations: LY294002 has off-target effects and is not an inhibitor specific to the entire PI3K–Akt–mTOR chain. Evidence access: Primary abstract Orthosilicic Acid Accelerates Bone Formation in Human Osteoblast-Like Cells Through the PI3K-Akt-mTOR Pathway. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30421162/ · DOI 10.1007/s12011-018-1574-9

cross_nutrient

Insulin (stimulus)

evidence_span

{"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 7141, "end_char": 7815, "text_sha256": "31871685ed5bb9ceb845b035d50807218311c0fad543f690e5ab924ba9872d0d"}

experimental_model

Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed

exposure

NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants

limitations

Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

The muscle response was accompanied by changes in insulin-signaling proteins.

primary_references

[nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

tissue_or_cell_type

Skeletal muscle, PBMCs, liver and adipose insulin sensitivity

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1501–1513

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed · source_derived_draft · unverified_draft

### nia-clin-nmn-muscle-signal Muscle insulin-stimulated AKT and mTOR phosphorylation and total abundance increased after NMN but not placebo. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The muscle response was accompanied by changes in insulin-signaling proteins. organism: Homo sapiens tissue_or_cell_type: Skeletal muscle, PBMCs, liver and adipose insulin sensitivity experimental_model: Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed limitations: Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit. exposure: NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants cross_nutrient: Insulin (stimulus) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 7141, "end_char": 7815, "text_sha256": "31871685ed5bb9ceb845b035d50807218311c0fad543f690e5ab924ba9872d0d"} [nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

evidence_span

{"source_cache": "artifacts/cold-research/31513450.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f39d3b6bef4879805e7aab7b14df67921ac12765af5d4466836936039ad7a872", "start_char": 0, "end_char": 2195, "text_sha256": "f39d3b6bef4879805e7aab7b14df67921ac12765af5d4466836936039ad7a872"}

experimental_model

Sixteen men completing seven weeks of whole-body resistance training with immersion or passive recovery

exposure

15 minutes at 10 degrees C after each session, three days a week for seven weeks

limitations

A second training study with molecular endpoints. It reproduces the fibre-size result but not the strength result, which is the disagreement recorded in this collection.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

The building signal was turned down, the breakdown marker went up, and the muscle stress proteins did not accumulate.

primary_references

[cold-p31513450] Cold water immersion attenuates anabolic signaling and skeletal muscle fiber hypertrophy, but not strength gain, following whole-body resistance training. (2019). https://pubmed.ncbi.nlm.nih.gov/31513450/ DOI: 10.1152/japplphysiol.00127.2019

tissue_or_cell_type

Skeletal muscle

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 845–856

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sixteen men completing seven weeks of whole-body resistance training with immersion or passive recovery · source_derived_draft · unverified_draft

### cold-cwi-anabolic-catabolic Post-exercise mTORC1 signalling measured as rps6 phosphorylation was blunted at 1 and 48 hours after training, basal FOXO1 protein content increased 1.3-fold, and training-induced increases in heat shock protein 27 were attenuated with reduced total heat shock protein 72. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The building signal was turned down, the breakdown marker went up, and the muscle stress proteins did not accumulate. organism: Human tissue_or_cell_type: Skeletal muscle experimental_model: Sixteen men completing seven weeks of whole-body resistance training with immersion or passive recovery limitations: A second training study with molecular endpoints. It reproduces the fibre-size result but not the strength result, which is the disagreement recorded in this collection. exposure: 15 minutes at 10 degrees C after each session, three days a week for seven weeks evidence_span: {"source_cache": "artifacts/cold-research/31513450.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f39d3b6bef4879805e7aab7b14df67921ac12765af5d4466836936039ad7a872", "start_char": 0, "end_char": 2195, "text_sha256": "f39d3b6bef4879805e7aab7b14df67921ac12765af5d4466836936039ad7a872"} [cold-p31513450] Cold water immersion attenuates anabolic signaling and skeletal muscle fiber hypertrophy, but not strength gain, following whole-body resistance training. (2019). https://pubmed.ncbi.nlm.nih.gov/31513450/ DOI: 10.1152/japplphysiol.00127.2019

evidence_span

{"source_cache": "artifacts/cold-research/26174323.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "91eff53ecc4779637af3d6fd47a67892729e3a896fdc8738f69d1c7936b4787d", "start_char": 0, "end_char": 1595, "text_sha256": "91eff53ecc4779637af3d6fd47a67892729e3a896fdc8738f69d1c7936b4787d"}

experimental_model

Twelve weeks of strength training in 21 men with immersion or active recovery, plus a biopsy study in nine men

exposure

10 minutes of cold water immersion after each training session, twice weekly for 12 weeks

limitations

A randomised training study with muscle biopsies. It measures long-term adaptation rather than acute recovery, which is why it can disagree with the soreness literature without contradicting it.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

The repair cells that build new muscle showed up in smaller numbers after the cold.

primary_references

[cold-p26174323] Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training. (2015). https://pubmed.ncbi.nlm.nih.gov/26174323/ DOI: 10.1113/jp270570

tissue_or_cell_type

Skeletal muscle

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 819–830

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve weeks of strength training in 21 men with immersion or active recovery, plus a biopsy study in nine men · source_derived_draft · unverified_draft

### cold-cwi-satellite-cells Satellite cells expressing NCAM and Pax7 increased 24 to 48 hours after exercise with active recovery, and numbers were greater after active recovery than after immersion, while phosphorylation of p70S6 kinase at Thr421/Ser424 increased after exercise in both conditions but was greater after active recovery. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The repair cells that build new muscle showed up in smaller numbers after the cold. organism: Human tissue_or_cell_type: Skeletal muscle experimental_model: Twelve weeks of strength training in 21 men with immersion or active recovery, plus a biopsy study in nine men limitations: A randomised training study with muscle biopsies. It measures long-term adaptation rather than acute recovery, which is why it can disagree with the soreness literature without contradicting it. exposure: 10 minutes of cold water immersion after each training session, twice weekly for 12 weeks evidence_span: {"source_cache": "artifacts/cold-research/26174323.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "91eff53ecc4779637af3d6fd47a67892729e3a896fdc8738f69d1c7936b4787d", "start_char": 0, "end_char": 1595, "text_sha256": "91eff53ecc4779637af3d6fd47a67892729e3a896fdc8738f69d1c7936b4787d"} [cold-p26174323] Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training. (2015). https://pubmed.ncbi.nlm.nih.gov/26174323/ DOI: 10.1113/jp270570

experimental_model

MDA-MB-231 and A549 cells.

limitations

A pathway readout does not establish a unique causal target or human anticancer efficacy.

nutrient_topic

EGCG collection; comparator and shared-pathway records retain their actual intervention. · Epigallocatechin-3-gallate (EGCG)

plain_language

Downstream growth signaling changed in the cell experiments.

primary_references

Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21300025/ · DOI 10.1016/j.bbrc.2011.02.010

EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 228–234

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · MDA-MB-231 and A549 cells. · source_derived_draft · unverified_draft

## egcg-akt Downstream growth signaling changed in the cell experiments. EGCG reduced AKT Ser473 phosphorylation alongside proliferation in the tested cancer cells. Model: MDA-MB-231 and A549 cells. Limitations: A pathway readout does not establish a unique causal target or human anticancer efficacy. Evidence access: primary abstract. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21300025/ · DOI 10.1016/j.bbrc.2011.02.010