Mitochondria-associated endoplasmic reticulum membrane (MAM)-associated calpains system in preeclampsia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41139197", "kind": "science-record", "revision": 4, "content_hash": "sha256:a79148b62725c88cd661ccf88d9d6231b610deba9c8e358a82f149fd117da574", "created_at": "2026-11-01T20:31:11Z", "updated_at": "2026-11-01T22:57:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mitochondria-associated endoplasmic reticulum membrane (MAM)-associated calpains system in preeclampsia.", "doi": "10.1186/s12884-025-08244-1", "pmid": "41139197", "authors": ["Cui Zhang", "Jingjing Jiang", "Hongfang Kong", "Xuyuan Ma", "Hong Xin"], "journal": "BMC pregnancy and childbirth", "year": 2025, "abstract": "BACKGROUND: Preeclampsia (PE) is a multisystem disorder characterized primarily by hypertension and proteinuria after 20 weeks of gestation, significantly impacting maternal and fetal health. The etiology remains unclear, but it is primarily attributed to placental dysfunction leading to systemic vascular endothelial damage and inflammatory responses. Mitochondria-associated endoplasmic reticulum membranes (MAMs) influence mitochondrial and endoplasmic reticulum (ER) function by regulating calcium homeostasis, autophagy, and apoptosis. In PE, mitochondrial dysfunction and ER stress have been widely observed. However, detailed investigations into the specific mechanisms and roles of MAMs in PE remain limited. Thus, this study aimed to investigate how MAM-associated biomarkers affect PE.\nMETHODS: The study involved 31 women with early-onset PE, 30 with late-onset PE, and 54 healthy controls matched for gestational age. Placental morphology and MAM structure in both PE and control tissues were assessed using Hematoxylin-Eosin (HE) staining and electron microscopy (EM). Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets (GSE190971, GSE24129) identified MAMs-related genes (MAMs-RGs) and candidate biomarkers through weighted gene co-expression network analysis (WGCNA), machine learning algorithms (Least absolute shrinkage and selection operator, Support Vector Machine Recursive Feature Elimination), and functional enrichment. Real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to validate biomarker expression in PE placentas. Calpain-1, calpain-2, and calpastatin expression levels were evaluated using Immunofluorescence and Western blotting techniques.\nRESULTS: The results showed early-onset PE (EOPE) had higher abnormal pregnancy history, fetal growth restriction, systolic/diastolic ratio, and lower placental growth factor than late-onset PE (LOPE) and controls. Both PE types had fewer placental villi, but EOPE showed more severe ultrastructural changes in mitochondria-associated membranes. Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01). Immunofluorescence and Western blotting showed calpain-1 and calpastatin were decreased in EOPE, while calpain-2 was reduced in both PE types, with calpain-1 increased in LOPE.\nCONCLUSIONS: EOPE is characterized by placental dysfunction, with increased MAM contact observed in PE placentas.The calpain-calpastatin system may be involved in placental dysfunction in PE, with calpain-2 downregulation observed in both PE subtypes and calpain-1 dysregulation differing between EOPE and LOPE. These changes are accompanied by increased MAM contacts in PE placentas, suggesting a potential link between MAM structural abnormalities and calpain system dysregulation, with calpain-2 levels potentially associated with disease severity.", "claims": [{"id": "claim-method", "statement": "Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets (GSE190971, GSE24129) identified MAMs-related genes (MAMs-RGs) and candidate biomarkers through weighted gene co-expression network analysis (WGCNA), machine learning algorithms (Least absolute shrinkage and selection operator, Support Vector Machine Recursive Feature Elimination), and functional enrichment.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41139197", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets (GSE190971, GSE24129) identified MAMs-related genes (MAMs-RGs) and candidate biomarkers through weighted gene co-expression network analysis (WGCNA), machine learning algorithms (Least absolute shrinkage and selection operator, Support Vector Machine Recursive Feature Elimination), and functional enrichment."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data is provided within the manuscript or supplementary information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41139197", "locator": "sections[22] \"Data availability\" paragraph 2", "quote": "Data is provided within the manuscript or supplementary information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01).", "kind": "quantitative", "target": {"value": 0.01, "unit": "p-value", "tolerance": null, "source": "Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01)."}, "evidence": [{"asset": "source:pmid:41139197", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41139197"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE190971"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE190971"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41139197", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12884-025-08244-1", "sha256": "sha256:f01ef19d041e1d8934ad6c618d056542352a320353c06d91ebee0c360ceb0efc", "bytes": 45246, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12884-025-08244-1", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12553276", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE190971", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190971", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE190971", "version": null, "note": "Data is provided within the manuscript or supplementary information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data is provided within the manuscript or supplementary information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5736672", "GSM5736673", "GSM5736674", "GSM5736675", "GSM5736676", "GSM5736677", "GSM5736678", "GSM5736679", "GSM5736680", "GSM5736681", "GSM5736682", "GSM5736683", "GSM5736684", "GSM5736685", "GSM5736686", "GSM5736687", "GSM5736688", "GSM5736689", "GSM5736690", "GSM5736691", "GSM5736692", "GSM5736693", "GSM5736694", "GSM5736695", "GSM5736696", "GSM5736697", "GSM5736698", "GSM5736699", "GSM5736700", "GSM5736701", "GSM5736702", "GSM5736703", "GSM5736704", "GSM5736705", "GSM5736706", "GSM5736707", "GSM5736708", "GSM5736709", "GSM5736710", "GSM5736711", "GSM5736712"], "sample_count": 41, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "Transcriptomic analysis of placenta and its released extracellular vesicles in normal and preeclampsia pregnancies: insigths into novel biomarkers and mechanisms of disease", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE24129", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24129", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE24129", "version": null, "note": "Data is provided within the manuscript or supplementary information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data is provided within the manuscript or supplementary information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM594041", "GSM594042", "GSM594043", "GSM594044", "GSM594045", "GSM594046", "GSM594047", "GSM594048", "GSM594049", "GSM594050", "GSM594051", "GSM594052", "GSM594053", "GSM594054", "GSM594055", "GSM594056", "GSM594057", "GSM594058", "GSM594059", "GSM594060", "GSM594061", "GSM594062", "GSM594063", "GSM594064"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Gene expression profiling for placentas from pre-eclamptic, unexplained FGR and normal pregnancies.", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE190971 not downloaded", "asset:data:geo:GSE190971 licence not read", "asset:data:geo:GSE24129 not downloaded", "asset:data:geo:GSE24129 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets (GSE190971, GSE24129) identified MAMs-related genes (MAMs-RGs) and candidate biomarkers through weighted gene co-expression network analysis (WGCNA), machine learning algorithms (Least absolute shrinkage and selection operator, Support Vector Machine Recursive Feature Elimination), and functional enrichment."}}, {"id": "method-2", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"id": "method-3", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-4", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "Chi-square"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "bootstrap_mean_difference", "expected_value": 0.01, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: support_vector_machine."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE190971", "GSE24129"], "resolved_accessions": ["GSE190971", "GSE24129"], "statements": ["Data is provided within the manuscript or supplementary information files."], "basis": "The paper names GSE190971, GSE24129 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "assets": ["source:pmid:41139197", "data:geo:GSE190971"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE190971"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:04:01Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12855, "completion_tokens": 1833, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:41139197", "type": "paper", "label": "pmid:41139197"}, {"id": "source:pmid:41139197", "type": "manuscript", "label": "PMID 41139197 full text"}, {"id": "data:geo:GSE190971", "type": "dataset", "label": "GEO GSE190971"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41139197", "type": "paper", "label": "pmid:41139197"}, {"id": "source:pmid:41139197", "type": "manuscript", "label": "PMID 41139197 full text"}, {"id": "data:geo:GSE190971", "type": "dataset", "label": "GEO GSE190971"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41139197", "type": "extraction", "used": ["source:pmid:41139197"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE190971", "type": "accession_resolution", "used": ["data:geo:GSE190971"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:41139197", "parent_hash": "sha256:b111a4fd456aeec030229c70e7e4487b1060f661cc238f5d83208ea78db55c14", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE190971 licence not read", "asset:data:geo:GSE190971 not downloaded", "asset:data:geo:GSE24129 licence not read", "asset:data:geo:GSE24129 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["gulating calcium homeostasis, autophagy, and apoptosis. In PE, mitochondrial dysfunction and ER str"], "order_basis": "paper_text_order:591", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rse transcriptase-polymerase chain reaction (RT-qPCR) was used to validate biomarker expression i", "transcriptase-polymerase chain reaction (RT-qPCR) was used to validate biomarker expression i"], "order_basis": "paper_text_order:1578", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tatin expression levels were evaluated using Immunofluorescence and Western blotting techniques. RESULTS: Th", "ntly downregulated in PE samples (P < 0.01). Immunofluorescence and Western blotting showed calpain-1 and ca", "(PBS), and part was fixed in 4% formalin for immunofluorescence and hematoxylin-eosin (HE) staining analysis"], "order_basis": "paper_text_order:1723", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["were evaluated using Immunofluorescence and Western blotting techniques. RESULTS: The results showed earl", "E samples (P < 0.01). Immunofluorescence and Western blotting showed calpain-1 and calpastatin were decrea", "remaining samples were stored at − 80 °C for Western blotting. Additionally, a 1 mm × 1 mm tissue sample w"], "order_basis": "paper_text_order:1747", "id": "assay:4"}, {"role": "analysis", "definition_id": "machine_learning", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["train_classifier", "cross_validate", "roc_auc"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets (GSE190971, GSE24129) identified MAMs-related genes (MAMs-RGs) and candidate biomarkers through weighted gene co-expression network analysis (WGCNA), machine learning algorithms (Least absolute shrinkage and selection operator, Support Vector Machine Recursive Feature Elimination), and functional enrichment."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}