The Influence of Circulating Exosomes Derived From Younger and Older Donors on Hypoxia-Inducible Factor 1 Alpha Gene Expression and P21 Protein in Cord Blood Hematopoietic Stem Cells
Bibliographic record
Abstract
Background: Exosomes are a group of extracellular vesicles that are influential in intercellular signaling and can affect aging. Hypoxia-inducible factor 1¦Á (HIF-1¦Á) is the principal mediator in response to hypoxia and can regulate aging. Moreover, P21 is a part of the downstream signaling pathway of hypoxia and is elevated during aging. Therefore, this research was conducted to investigate the effect of plasma exosomes of younger and older individuals on the expression of HIF-1¦Á gene and P21 protein in hematopoietic stem cells (HSCs). Methods: Plasma exosomes were derived from older and younger men and were characterized. Then, HSCs were isolated from cord blood samples and treated with exosomes of older and younger men. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to evaluate cell viability. Next, the expression of HIF-1¦Á gene and P21 protein were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Results: HIF-1¦Á gene expression was considerably increased in HSCs treated with 10 µg/mL of exosomes isolated from younger men (Y10-Exo) compared to the untreated group (P = 0.002). Moreover, HIF-1¦Á gene expression was remarkably decreased in HSCs treated with 10 µg/mL of exosomes obtained from older men (O10-Exo) in comparison with the untreated group (P < 0.001). Additionally, the expression of P21 protein was significantly increased in HSCs treated with 5 µg/mL of exosomes derived from older individuals (O5-Exo) and O10-Exo compared to the untreated group (P = 0.000 and P = 0.002, respectively). Conclusions: Our findings showed that exosomes isolated from younger participants cause elevation in HIF-1¦Á and may lead to delayed aging in HSCs. In addition, exosomes isolated from older participants can probably lead to aging through the reduction in HIF-1¦Á and elevation in P21. J Hematol. 2024;13(5):192-199 doi: https://doi.org/10.14740/jh1291
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".