A SELECTIVE SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 INHIBITOR ALLEVIATES THE MURINE LUPUS
Bibliographic record
Abstract
PV259 / #49 Poster Topic: AS24 - SLE-Treatment Background/Purpose The Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor crucial for regulating gene expression. It can be activated by various cytokines, which are implicated in the development of systemic lupus erythematosus (SLE). Studies have demonstrated the efficacy of inhibiting the Janus-activated kinase (JAK)/STAT3 pathway in both lupus animal models and patients. However, many existing STAT3 inhibitors lack specificity, complicating efforts to attribute the observed effects exclusively to STAT3 inhibition. In this study, we examined a novel small molecule selectively inhibits STAT3 (HCB-5018), could ameliorate disease severity by downregulation of STAT3 in MRL/lpr lupus-prone mice. Methods MRL/lpr mice were orally administered HCB-5018 from 14 to 18 weeks of age, 5 days a week for 4 weeks, followed by the collection of serum, urine, and tissue samples for analysis. The major organs associated with SLE, including the spleen, lymph nodes, and kidneys, were analyzed. Serum ELISA analysis was conducted to measure key indicators of SLE and inflammatory cytokines. Enzyme-linked immunosorbent assays, histological analysis, immunohistochemical staining, and western blotting were performed to evaluate key markers of SLE and protein expression. Results Mice treated with HCB-5018 exhibited improvements in the manifestations of the SLE, with decreased levels of anti-dsDNA antibodies and inflammatory cytokines such as IL-17 and increased levels of C3 complement than vehicle-treated mice. HCB-5018-treated mice exhibited significantly lower urine albumin levels. In addition, histopathological analysis of kidney tissue confirmed that HCB-5018 decrease in the number of mesangial cells, proliferation of endothelial cells, and infiltration of inflammatory cells around the glomeruli in MRL/lpr mice. Furthermore, a significant reduction in the expression of phosphorylated STAT3 was observed in the lymph nodes, spleen and kidney of mice treated with HCB-5018. Conclusions These results suggest that the STAT3 pathway is implicated in lupus progression in mice and that selective targeting of STAT3 is effective in alleviating the development of murine lupus. Therefore, HCB-5018 represent a potential candidate for novel therapeutic strategies for SLE management through selective STAT3 inhibition.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".