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Record W3212437926 · doi:10.21203/rs.3.rs-35501/v1

Periodic Curcumin Monoglucuronide Injections Ameliorate Structural Osteoarthritis Changes in Rats with Destabilized Medial Meniscus

2020· preprint· en· W3212437926 on OpenAlexaff
Akihiro Nakahata, Akira Itô, Ryo Nakahara, Atsuhiro Kishimoto, Atsushi Imaizumi, Tadashi Hashimoto, Shogo Mukai, Yasuaki Nakagawa, Hiroshi Kuroki

Bibliographic record

VenueResearch Square (Research Square) · 2020
Typepreprint
Languageen
FieldMedicine
TopicOsteoarthritis Treatment and Mechanisms
Canadian institutionsDebiopharm Group (Canada)
FundersJapan Society for the Promotion of Science
KeywordsCurcuminOsteoarthritisMedial meniscusMedicineSalineCartilageMeniscusHistologyIn vivoImmunohistochemistryArticular cartilageInflammationUrologyPathologyInternal medicinePharmacologyAnatomy

Abstract

fetched live from OpenAlex

Abstract Background: Curcumin has anti-inflammatory effects. However, curcumin is poorly water-soluble, and when administered orally, formscurcumin conjugates with poor efficacy.Curcumin monoglucuronide (TBP1901) is highly water-soluble and can existinthe free-form in a greater proportion than curcumin in vivo. This study aimed to evaluate the effectiveness of intra-articular TBP1901 injections fora rat model of osteoarthritis (OA). Methods: Sixty-four male Wistar rats (12weeks old) that had receivedthe destabilized medial meniscus(DMM) surgery, were randomly separatedinto the TBP1901 injectionandthe saline solution injection (control) group. They were sacrificedat 1, 2, 6, or 10weeks postoperatively(n = 8 for each). The TBP1901 (30mg/mL) andsaline solutionof 50μLwere administered to the knee joint through the patella tendon twice a week for the rats sacrificedat1 and 2weeks or once a week for at6 and 10weeks. The OA changes were evaluated by micro-computed tomography (micro-CT), histology, and immunohistochemical analysis. Results: Curcumin fluorescence was confirmed in the articular cartilageand synovium of rats with TBP1901 injections at all observation periods.The TBP1901injections significantly reducedthe synovial inflammation at 1 and 2 weeks and the expression of TNFα in thetibialarticular cartilage at 6 weeks postoperatively.Moreover, TBP1901 injections ameliorated the articular cartilage structure, the subchondral bone (SB) plate thickness, and perforations from 6 to 10 weeks.As a result, there were significant differencesbetween groups in OA scores, SB plate thickness, and perforations at 10 weeks postoperatively.In addition, osteophyte formation in the TBP1901group was significantly suppressed after 10 weeks. Conclusion: This study reports the first evidence that TBP1901 injections suppress inflammation and osteophyte formation, and ameliorate the articular cartilage and SB pathologies by absorption in the articular cartilage and synovium in a rat DMM model.Therefore, intra-articular injections of TBP1901may be effective in improving OA pathology.

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)0.005
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesMeta-epidemiology (narrow)
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 score0.296
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0050.002
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0040.004
Science and technology studies0.0010.002
Scholarly communication0.0010.000
Open science0.0010.003
Research integrity0.0010.010
Insufficient payload (model declined to judge)0.0020.000

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 head0.094
GPT teacher head0.401
Teacher spread0.307 · 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; both teacher heads agree on what is shown here.

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

Citations1
Published2020
Admission routes1
Has abstractyes

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