Incredible. I do 50 000iu per day with 1g mag wich is needed to activate D
(edit: only two links can be posted in the same post - check more bellow)
Vitamin D A new player in the world of mTOR signaling | Request PDF
pretty bad to need 3 posts for this admin
So its a senolytic in other words, will mop the floor with quercetn/fisetin
An analysis of the first paper. I’m not sure how relevant this is for most of us, it’s in-vitro, and focused on carcinomas.
Analysis from CGPT5
Here’s a structured, evidence-based appraisal of the article you shared:
Paper: Provvisiero DP et al. “Vitamin D reverts resistance to the mTOR inhibitor everolimus in hepatocellular carcinoma through the activation of a miR-375/oncogenes circuit.” Scientific Reports (2019) s41598-019-48081-9. (Nature)
1) Journal reputation & indexing
- Peer review & scope. Scientific Reports (Nature Portfolio) is a large, peer-reviewed open-access “mega-journal” that judges manuscripts primarily on technical soundness rather than novelty. (Wikipedia)
- Indexing. The journal is indexed in Web of Science, PubMed/MEDLINE, PubMed Central, Scopus, DOAJ, and others. (Nature)
- Impact/metrics (context). 2024 Journal Impact Factor ≈ 3.9; 5-year IF ≈ 4.3. (Useful for context only; not a quality guarantee.) (Nature)
Takeaway: A reputable, widely indexed venue with rigorous but “soundness-focused” review criteria (not a selective, high-novelty journal). (Wikipedia)
2) Article content & methods
a) Study design
- Model: strictly in-vitro HCC models; authors created everolimus-resistant (EveR) lines by chronic exposure (≥4 months) in PLC/PRF/5 and JHH-6; HepG2 EveR was generated but not used for the core analyses because resistance did not differ from parental cells. (Nature)
- Interventions: calcitriol (1,25(OH)\₂D₃) at 10⁻⁷ M; everolimus at 10⁻¹⁴ to 10⁻⁸ M; vehicles kept at 0.04%. (Nature)
- Assays: DNA content & colony formation for proliferation/survival; Western blot & immunofluorescence for EMT markers; qPCR (miRNA array and targeted); luciferase reporter to validate miR-375 binding to c-MYC (5′UTR); miR-375 mimic/inhibitor gain/loss-of-function. (Nature)
b) Validity of methods
- The resistance model (long-term drug exposure) is standard for mechanistic studies. The miRNA causal chain(VitD → ↑miR-375 → ↓MTDH/YAP-1/c-MYC → resensitization) is probed with orthogonal tools (array screen → qPCR → luciferase → mimic/inhibitor), which strengthens internal validity. (Nature)
- Limitations: entirely cell-based (no in-vivo data, no patient samples); everolimus concentrations are lower than typical clinical exposures (authors note this), which may limit translational relevance; WB experiments replicated twice, less robust than triplicate biological repeats used elsewhere in the paper. (Nature)
c) Data quality & statistics
- Authors state quadruplicate experiments, replicated three times (except WB, twice). ANOVA with multiple-comparison corrections (Bonferroni/Newman-Keuls/Dunnett) via SPSS and GraphPad. This is acceptable for in-vitro work, though effect sizes and exact n’s per figure aren’t always explicit. (Nature)
d) Conclusions: objectivity & support
- Main claim: calcitriol re-sensitizes everolimus-resistant HCC cells by up-regulating miR-375, which down-regulates MTDH, YAP-1, and c-MYC, and partly reverses EMT features. The data presented (functional assays + target validation) support this within the in-vitro context. Authors appropriately acknowledge that in-vitro only is a limitation and suggest future in-vivo work. (Nature)
3) References: relevance & currency
- Citations span clinical HCC therapy, mTORi trials (including EVOLVE-1 everolimus failure), EMT/drug-resistance literature, and miRNA biology, with many sources from 2008–2018 (appropriate for a 2019 paper). (Nature)
- Overall, the bibliography is technically relevant and reasonably current for the time of publication.
4) Author credibility & conflicts
- Affiliations: University of Naples “Federico II,” Departments of Endocrinology and Public Health (academic lab setting). (Nature)
- Funding: “This work was not supported by any grant.” (Neutral for bias; does imply resource limits.)
- COI: “The authors declare no competing interests.”
5) How this paper should influence prior knowledge & its strength
- What it adds: Mechanistic evidence that vitamin D (calcitriol) may overcome mTOR-inhibitor resistance in HCC via a miR-375–MTDH/YAP-1/c-MYC axis and partial EMT reversal. This extends prior observations that vitamin D and miRNAs modulate cancer phenotypes. (Nature)
- Strength of influence: Hypothesis-generating / preclinical. Because the work is in-vitro only, with no animal efficacy or clinical correlation, it should modestly shift priors—encouraging in-vivo validation and biomarker-driven studies, but not changing clinical practice or guidelines by itself. Authors explicitly position it as a foundation for future in-vivo work. (Nature)
Bottom line
- Scientific Reports is a peer-reviewed, widely indexed journal; the article meets standard technical-soundnesscriteria. (Nature, Wikipedia)
- The experimental logic is coherent and multifaceted; statistics are standard for cell studies; COI absent. (Nature)
- Key limitations—entirely in-vitro design, some modest replication depth, and use of sub-clinical drug concentrations—mean the findings should inform mechanism and future preclinical/clinical hypotheses, rather than directly influence clinical care. (Nature)
If you’d like, I can tabulate the paper’s risk-of-bias items (model selection, blinding, replication, reagent validation, statistics) and compare them with ARRIVE/NIH rigor guidelines to give you a scorecard-style summary.
Wich is why i included so many of the studies and not just one
Have you read these studies / papers already? Why did you find them compelling? What do you think is the important message you’ve found in reading these papers? Please don’t just post a bunch of links to papers. There are millions of papers in Pubmed and we have no interest in people just copying them here into our forum without good reason. Your reasoning and rationale is not at all clear.