September 2026 Literature Digest | abinScience Antibodies and Recombinant Proteins in ESCC, PAH, Alzheimer’s Disease and HFpEF Research

Esophageal squamous cell carcinoma (ESCC) is usually asymptomatic in its early stages and is often diagnosed at an advanced stage. Endoscopic biopsy, the current standard, is invasive and unsuitable for large-scale screening, so non-invasive biomarkers for early detection are needed. Tumor-associated autoantibodies are stable and can appear before clinical symptoms, but previous studies have mostly relied on known antigens and therefore had limited coverage. This study used phage immunoprecipitation sequencing (PhIP-Seq) covering the entire human proteome to perform unbiased autoantibody profiling of more than 1,000 plasma samples from three hospitals. ESCC patients showed an overall increase in autoantibody reactivity, and the differential antigens were enriched in pathways related to epigenetic regulation, transcription and the cytoskeleton. Using three feature selection methods, the researchers identified 18 core antigen peptides (including KMT2C, INPP4B and NY-ESO-1, several of which are reported for the first time) and used them to build an XGBoost diagnostic model. The model showed good discriminative performance in internal validation, external validation and a nested case-control cohort of samples collected before diagnosis, and performed better in early-stage than in late-stage patients. In addition, some peptides differed between patients who did and did not achieve complete response after chemoradiotherapy. The authors consider the model a new approach for non-invasive early screening and treatment monitoring of ESCC, but note that it still requires validation in larger prospective cohorts and on other detection platforms.

Pulmonary arterial hypertension (PAH) is closely associated with metabolic reprogramming of endothelial cells, impaired mitochondrial quality control and redox imbalance. Spermidine (SPD) is known to have cardiovascular protective effects, but its effect on endothelial metabolism in PAH and its target remain unclear. This study used monocrotaline-induced PAH rats and palmitic acid-stimulated pulmonary microvascular endothelial cells as models, combining metabolomics, lipidomics and molecular biology methods. SPD lowered pulmonary arterial pressure and reduced right ventricular remodeling, vascular remodeling and endothelial injury. Under lipotoxic conditions, SPD reduced lipid accumulation, restored fatty acid β-oxidation (FAO) and mitochondrial respiration, lowered mitochondrial reactive oxygen species and lipid peroxidation, corrected lipid abnormalities dominated by phosphatidylethanolamine, inhibited PLIN2–vimentin-associated endothelial-to-mesenchymal transition, and promoted mitophagy. Biophysical experiments supported direct binding of SPD to HADHA, the α subunit of the mitochondrial trifunctional protein, which stabilized the protein, while HADHA knockdown weakened several of the protective effects of SPD. The authors conclude that HADHA is involved in mediating the protective effect of SPD on the PAH endothelium, although whether SPD directly enhances HADHA enzymatic activity remains to be verified.

Mitochondrial dysfunction is one of the earliest pathological features of Alzheimer's disease (AD), but how β-amyloid (Aβ) causes mitochondrial damage in the early stages of the disease is not yet clear. This study used APP/PS1 mice and HT22 neuronal cells as models, combining proteomics, targeted metabolomics and in vivo and in vitro genetic interventions. Proteomics showed marked changes in mitochondria-related pathways in the cortex and hippocampus of early-stage AD mice, with malic enzyme 3 (Me3) consistently upregulated across all AD groups; metabolomics indicated that APP overexpression restricted glycolysis and disrupted the TCA cycle. Further experiments confirmed that Me3 colocalizes and directly binds with Aβ42 in mitochondria, with the binding site located in the NAD(P)-binding domain of Me3, leading to reduced enzymatic activity, increased reactive oxygen species, mitochondrial fragmentation and blocked mitophagy. Knockdown of Me3 alleviated these defects in both cells and mice. The authors conclude that Aβ42–Me3 co-aggregation is a key link between Aβ pathology and early mitochondrial dysfunction, and that selectively blocking this interaction is a more suitable intervention strategy than global inhibition of Me3, although the findings still need to be validated in human samples.

Heart failure with preserved ejection fraction (HFpEF) accounts for about half of all heart failure cases, and effective targeted therapies are currently lacking. Tectorigenin (Tec) is an isoflavone derived from traditional Chinese medicine that has shown multiple cardioprotective effects in previous studies, but its efficacy and mechanism in HFpEF are unclear. This study used HFpEF mice induced by a high-fat diet combined with L-NAME, and palmitic acid-treated cardiomyocytes, as models. Whether administered during disease development or after the model was established, Tec improved diastolic function in mice and reduced myocardial fibrosis, hypertrophy, pulmonary congestion and the decline in exercise tolerance; at the cellular level, it reduced lipotoxicity-induced apoptosis, lipid accumulation and oxidative stress. Transcriptomic analysis showed that Tec mainly improved myocardial fatty acid metabolism and significantly upregulated Acot1, a gene that regulates lipid metabolism. Mechanistically, Tec directly binds EGFR and inhibits its aberrant activation, which downregulates the transcription factor EGR2 and relieves EGR2-mediated transcriptional repression of the Acot1 promoter. Cardiomyocyte-specific knockdown of Acot1 or activation of EGFR weakened the protective effect of Tec, and the same regulatory relationship was observed in human iPSC-derived cardiomyocytes. The authors conclude that Tec improves myocardial lipid metabolism and alleviates HFpEF through the EGFR–EGR2–Acot1 axis.