Piperine inhibits the proliferation of colorectal adenocarcinoma by regulating ARL3-mediated endoplasmic reticulum stress.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38972051", "kind": "science-record", "revision": 2, "content_hash": "sha256:3e39482f98d82ee1de30bd8f36f49bb4414e2379ba2b49e5cb9571dee58e5cf2", "created_at": "2026-11-01T10:25:48Z", "updated_at": "2026-11-01T14:01:32Z", "generator": {"name": "corpus-assay-engine", "converter": "sep_to_sci_v1", "source_package_schema": "urn:bntrg:sep:1.0.0"}, "paper": {"state": "partial", "title": "Piperine inhibits the proliferation of colorectal adenocarcinoma by regulating ARL3-mediated endoplasmic reticulum stress.", "doi": "10.17305/bb.2024.10525", "pmid": "38972051", "authors": null, "journal": "Biomolecules & biomedicine", "year": 2025, "abstract": null, "claims": [{"id": "claim-1", "statement": "the headline numerical result the paper states for its main finding", "kind": "qualitative", "state": "blocked", "target": {"value": null, "unit": null, "tolerance": null, "source": null}, "evidence": []}], 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"source:pmid:38972051", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.17305/bb.2024.10525", "sha256": "sha256:cb1f4880a42866e4bb158d938e17559a190699788f37e891ffdcfa49a4cdeee8", "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.17305/bb.2024.10525", "version": null, "note": "Source read by the package builder: full_text.", "structure": {"access_state": "full_text"}}, {"id": "asset:table:pmid:38972051:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:03ffd2e24e512e1397bc40b0f74eee6597871ae546f629557844e54547d3d8e7", "bytes": 1419, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[24]/table-wrap[1]#TB1", "version": null, "note": "Comparison of characteristics of the COAD patients with high and low ARL3 expression", 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["capability"]}, "readiness": {"state": "partial", "tier": null, "blocking_axis": null, "blocked_on": null, "axes": {}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:38972051", "asset:table:pmid:38972051:1"], "steps": ["read_published_estimate"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": ["xml"], "capabilities": [], "data_gaps": ["source:pmid:38972051"]}, "gaps": ["corpus_record_absent"]}, "review": {"state": "partial", "machine_critique": {"status": "blocked", "providers": [{"provider": "minimax", "model": "MiniMax-M3.1-Flash", "prompt_version": "full-text-reading-v1", "prompt_hash": "52f57c0e12e645a8828e1bd786a8f69f19d64ae46cc55edbc8136443d6e57ed1", "source_hash": "cb1f4880a42866e4bb158d938e17559a190699788f37e891ffdcfa49a4cdeee8", "raw_response_sha256": "sha256:49bf3b3bcc9b875b6415b0eb9a5361cf10020d6648d8b61a4925df167d0b1e81", "raw_response_chars": 5660}, {"provider": "minimax_alt", "model": "MiniMax-M3", "prompt_version": "full-text-reading-v1", "prompt_hash": "ee54319b405d2aa042ee7254c5e97b6cadba5541e967fc3f0f234a796cb536d7", "source_hash": "cb1f4880a42866e4bb158d938e17559a190699788f37e891ffdcfa49a4cdeee8", "raw_response_sha256": "sha256:d69c00d1df3341cfe8d361948536a4f6623b85a3d8f640596a2fa3f90f6279d1", "raw_response_chars": 39384}], "target_providers": [{"provider": "minimax", "model": "MiniMax-M3.1-Flash", "prompt_version": "replication-target-v2", "prompt_hash": "b57399ed32180967a2e451e5db3ad798576b288b286e18c500b7240e6ce740b4", "source_hash": "cb1f4880a42866e4bb158d938e17559a190699788f37e891ffdcfa49a4cdeee8", "raw_response": "{\"parent_value\":0,\"unit\":\"\",\"evidence\":\"\",\"target_result\":\"No headline numerical result is stated for the main finding. The text instead reports that Piperine inhibited COAD cell proliferation in a concentration- and time-dependent manner, induced S-phase cell cycle arrest and apoptosis, downregulated ARL3 expression, suppressed TGF-β-induced EMT, and attenuated ARL3-mediated ER stress.\",\"number_stated\":false}", "reading": {"parent_value": 0, "unit": "", "evidence": "", "target_result": "No headline numerical result is stated for the main finding. The text instead reports that Piperine inhibited COAD cell proliferation in a concentration- and time-dependent manner, induced S-phase cell cycle arrest and apoptosis, downregulated ARL3 expression, suppressed TGF-β-induced EMT, and attenuated ARL3-mediated ER stress.", "number_stated": false, "source_locator": null}, "recorded_at": "2026-10-31T15:17:19.317882+00:00"}, {"provider": "minimax_alt", "model": "MiniMax-M3", "prompt_version": "replication-target-v2", "prompt_hash": "77440e9e7cc1a27bd2e1b86e3cc521f1de5e28d69a84fdf2f6b44b4a3e570b42", "source_hash": "cb1f4880a42866e4bb158d938e17559a190699788f37e891ffdcfa49a4cdeee8", "raw_response": "<think>We need answer JSON object. Need inspect source. User asks single numerical result replication registered target headline numerical result paper states for main finding. Source is abstract/conclusion, no specific headline numerical result except P&lt;0.05, maybe thresholds, datasets names contain numbers (GSE39582 etc). Need determine no number for registered target, output false parent 0 unit/evidence empty and target_result say what text states instead. Need ensure exact schema, JSON valid. We need reason whether \"P &lt; 0.05\" is a numerical result? Registered target headline numerical result paper states for main finding. The source doesn't state actual result value, only qualitative findings and statistical threshold. They explicitly instruct if text states no number for registered target, false. likely answer.\n\nNeed formulate target_result perhaps \"The text states that Piperine inhibits COAD cell proliferation in a concentration- and time-dependent manner, induces S-phase arrest and apoptosis, downregulates ARL3, suppresses TGF-β-induced EMT, and attenuates ARL3-mediated ER stress; it reports only a statistical-significance threshold (P &lt; 0.05), not a headline numerical result.\" Is mentioning P &lt; 0.05 potentially evidence? unit empty. They ask say what text does state instead. We can state no numerical result, qualitative findings. Need perhaps avoid quote requirement irrelevant when false. JSON only.\n\nLet's parse wording: \"Read supplied paper text and find the single numerical result that a replication of the registered target has to reproduce. Report the headline number only: the value the paper itself states for the registered target, not a value you calculated, converted, averaged or reconstructed. The unit must be the unit the paper prints. The evidence must be an exact, contiguous quotation from SOURCE TEXT that contains the number; do not shorten it, do not add an ellipsis and do not paraphrase it. Attribution may be carried by text's own wording... If text states no number for registered target, set number_stated to false, leave parent_value at 0, leave unit and evidence empty, and say in target_result what the text does state instead. Never invent a source.\"\n\nSource has \"P &lt; 0.05\" and \"mean ± standard deviation (SD)\" but no headline numerical effect. Need false. target_result could be concise: \"No headline numerical result is stated; the text reports that Piperine treatment inhibited COAD cell proliferation in a concentration- and time-dependent manner, reduced Ki-67 levels and colony-forming ability, induced S-phase arrest and apoptosis, downregulated ARL3, suppressed TGF-β-induced EMT, and attenuated ARL3-mediated ER stress.\" This is based text. Should we mention P threshold? They ask what text states instead perhaps state qualitative findings, not threshold perhaps threshold is numerical but not target result. Could include \"It reports qualitative findings ... and gives P &lt; 0.05 only as the statistical-significance threshold.\" This makes clear. Evidence empty exactly.\n\nNeed output required fields. parent_value number 0. unit \"\". evidence \"\". number_stated false. target_result string. Ensure no extra properties. Could target result quote? No need. Let's formulate.\n\nBut need consider possibility registered target \"headline numerical result the paper states for its main finding\" perhaps abstract omitted results section and numerical result is P&lt;0.05? They may expect find \"P &lt; 0.05\" as only numerical result? Let's deeply assess task patterns. This likely benchmark asks extract target number from paper source, often registered target generated from article metadata, source text perhaps abstract. Need identify numeric headline result. Here source text explicitly includes no percentages or quantitative values, only \"P &lt; 0.05\" in statistical analysis. Instructions emphasize if no number, false. So yes.\n\nNeed perhaps target_result say \"The text reports qualitative effects of Piperine ... but no numerical headline result for the main finding.\" Good.\n\nLet's ensure JSON escapes perhaps no special issue. Final only JSON.</think>\n\n{\"parent_value\":0,\"unit\":\"\",\"evidence\":\"\",\"target_result\":\"No headline numerical result is stated for the main finding. The text reports that Piperine treatment inhibited COAD cell proliferation in a concentration- and time-dependent manner, reduced Ki-67 levels and colony-forming ability, induced S-phase cell-cycle arrest and apoptosis, downregulated ARL3 expression, suppressed TGF-β-induced EMT, and attenuated ARL3-mediated ER stress; P < 0.05 is given only as the statistical-significance threshold.\",\"number_stated\":false}", "reading": {"parent_value": 0, "unit": "", "evidence": "", "target_result": "No headline numerical result is stated for the main finding. The text reports that Piperine treatment inhibited COAD cell proliferation in a concentration- and time-dependent manner, reduced Ki-67 levels and colony-forming ability, induced S-phase cell-cycle arrest and apoptosis, downregulated ARL3 expression, suppressed TGF-β-induced EMT, and attenuated ARL3-mediated ER stress; P < 0.05 is given only as the statistical-significance threshold.", "number_stated": false, "source_locator": null}, "recorded_at": "2026-10-31T15:17:26.132537+00:00"}], "agreement": false, "disagreements": {"target_result": {"minimax": "No headline numerical result is reported in the supplied text. The main finding is that Piperine inhibits colorectal adenocarcinoma cell proliferation and exerts anti-cancer effects by downregulating ARL3, inducing S-phase arrest and apoptosis, suppressing EMT, and attenuating ARL3-mediated endoplasmic reticulum stress.", "minimax_alt": "unknown (no headline numerical value is reported); Piperine treatment inhibited COAD cell proliferation in a concentration- and time-dependent manner, as indicated by reduced Ki-67 levels and decreased colony-forming ability.", "decisive": false}, "physical_methods": {"minimax": ["Immunohistochemistry using Human Protein Atlas data", "Cell proliferation assay", "Colony-forming assay", "Ki-67 measurement", "Cell-cycle analysis", "Apoptosis assay", "Western blot analysis of Bax, Bcl-2, cleaved caspase-3, cleaved PARP, BiP, p-IRE1α, ATF6, and CHOP", "Piperine treatment of COAD cells", "TGF-β-induced EMT analysis"], "minimax_alt": ["COAD cells were treated with Piperine, and in vitro assays evaluated cell proliferation, apoptosis, EMT marker expression, and ER stress (ERS) responses.", "Piperine treatment inhibited COAD cell proliferation in a concentration- and time-dependent manner, as indicated by reduced Ki-67 levels and decreased colony-forming ability.", "Piperine induced S-phase cell cycle arrest and facilitated apoptosis in COAD cells, evidenced by changes in Bax, Bcl-2, cleaved caspase-3, and cleaved Poly (ADP-ribose) polymerase (PARP) levels.", "Moreover, Piperine downregulated ARL3 expression in COAD cells, thereby suppressing transforming growth factor beta (TGF-β)-induced EMT.", "Additionally, Piperine attenuated the ARL3-mediated ER stress response, significantly reducing binding immunoglobulin protein (BiP), inositol-requiring enzyme 1 alpha (p-IRE1α), activating transcription factor 6 (ATF6), and C/EBP homologous protein (CHOP) levels."], "decisive": false}, "analysis_methods": {"minimax": ["Bioinformatics analysis of The Cancer Genome Atlas (TCGA)–COAD, GSE39582, and GSE44861 datasets", "Prognostic and clinicopathological association analysis", "R statistical analysis using the Limma package"], "minimax_alt": ["Bioinformatics analysis of The Cancer Genome Atlas (TCGA)–COAD, GSE39582, and GSE44861 datasets assessed ARL3 expression levels.", "Immunohistochemical data from the Human Protein Atlas (HPA) database confirmed ARL3 overexpression in COAD.", "The association of ARL3 with COAD clinical parameters and prognosis was also examined.", "Statistical analysis was performed using the R program with the R package “Limma.”"], "decisive": false}, "statistical_method": {"minimax": "For comparisons between two independent groups, the student's t-test was used. Multiple-group comparisons used one-way ANOVA paired with the Tukey post hoc test, and non-parametric paired data were analyzed with the Wilcoxon matched pairs signed rank test.", "minimax_alt": "The paper reports R with the “Limma” package, student’s t-test for comparisons between two independent groups, one-way ANOVA paired with the Tukey post hoc test for multiple-group comparisons, and the Wilcoxon matched pairs signed rank test for non-parametric paired data; significance was defined as P < 0.05. The supplied text does not explicitly map one of these methods to the unavailable headline numerical target.", "decisive": true}}, "agreement_basis": {"policy": "decisive_fields", "decisive_fields": ["work_type", "number_stated", "parent_value", "unit"]}, "blinded": true}, "human_critique": {"status": "not_run", "reviewer": null, "signed_at": null, "conflict_checked": false, "commentary": null}, "stages": [{"key": "target_materials", "status": "pending", "reason": null, "evidence": null}, {"key": "independent_readings", "status": "blocked", "reason": "The independent readings are incomplete or disagree; the source evidence must resolve the difference.", "evidence": {"provider_errors": []}}, {"key": "source_resolution", "status": "pending", "reason": null, "evidence": null}, {"key": "protocol_reconstruction", "status": "pending", "reason": null, "evidence": null}, {"key": "control_execution", "status": "pending", "reason": null, "evidence": null}, {"key": "control_comparison", "status": "pending", "reason": null, "evidence": null}, {"key": "publication", "status": "pending", "reason": null, "evidence": null}], "gaps": ["review.human_critique", "review.machine_critique.blocked"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "package:b53c78f75fe7b2cf6e22d34ac226a68b245b7cd3e9e5d17537701839d4922d9c", "type": "sep_package", "label": "SEP v1 package for pmid:38972051"}], "activities": [{"id": "activity:conversion:pmid:38972051", "type": "conversion", "used": ["package:b53c78f75fe7b2cf6e22d34ac226a68b245b7cd3e9e5d17537701839d4922d9c"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:minimax", "type": "model", "label": "minimax"}, {"id": "agent:minimax_alt", "type": "model", "label": "minimax_alt"}, {"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}], "source_run_id": "run-20261023T122449232913", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:38972051", "parent_hash": "sha256:5f9ca2ceb64b2aff88d91e983c51e028c207814fb5bfb1661d837de0a33a7692", "fork_of": null, "generation": 2}, "gaps": ["abstract", "asset:source:pmid:38972051 not verified", "authors", "capability", "corpus_record_absent", "execution.not_run", "method", "review.human_critique", "review.machine_critique.blocked", "step:obtain_source_data blocked on data:not_downloaded", "step:run_analysis blocked on no owned computational capability is bound to this experiment", "step:run_analysis input 'materials:the source data behind the published result in pmid:38972051' does not resolve to a declared asset", "targets"]}