Clinical And Experimental Medicine[JOURNAL]
Sun
200 papers
ITM2A promotes thyroid cancer differentiation through metabolic reprogramming and enhances PD-L1-dependent T-cell responses.
Sun W, Xiang C, Wang Y
Clin Exp Med · 2026 Jun · PMID 42332082 · Publisher ↗
The differentiation status of thyroid cancer (THCA) is closely associated with prognosis; however, the underlying molecular regulatory mechanisms remain incompletely understood. This study aimed to identify hub genes ass...
The differentiation status of thyroid cancer (THCA) is closely associated with prognosis; however, the underlying molecular regulatory mechanisms remain incompletely understood. This study aimed to identify hub genes associated with THCA differentiation based on progression-free interval (PFI)-related genes and to explore the underlying mechanisms. The common database datasets were integrated to identify differentially expressed genes, and univariate Cox regression analysis was performed to determine PFI-related genes. Molecular subtypes were constructed using consensus clustering based on PFI-related genes, and the differentiation status of different subtypes was evaluated. Hub genes were subsequently identified using least absolute shrinkage and selection operator (Lasso) regression and multivariate Cox regression analyses. In vitro experiments were conducted to validate the role of the hub gene in regulating dedifferentiation. Two PFI-related molecular subtypes were identified in this study. Cluster 2 exhibited a higher thyroid differentiation score (TDS), more favorable PFI outcomes, and metabolic features predominantly characterized by oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). ITM2A was identified as a hub gene. High expression of ITM2A promoted differentiation of THCA cells, suppressed malignant characteristics, and drove a metabolic shift from glycolysis toward FAO. In addition, ITM2A counteracted TGF-β-induced dedifferentiation and epithelial-mesenchymal transition, and enhanced antigen presentation as well as PD-L1-dependent T-cell responses. ITM2A maintained the differentiated state of THCA through metabolic reprogramming and shaped an immunologically favorable microenvironment, suggesting that it may serve as a potential biomarker for prognosis prediction and a therapeutic target for optimizing immunotherapy strategies.
Patient-derived tissue slice cultures from endoscopic biopsies as a translational ex vivo model for inflammatory bowel diseases.
Werner J, Schiller L, Müller C … +6 more , Lehmann J, Przybilla J, Schlosser T, Hoffmeister A, Kallendrusch S, Vissiennon C
Clin Exp Med · 2026 Jun · PMID 42329475 · Full text
Effective inflammatory bowel disease (IBD) management increasingly relies on patient-stratified therapeutic approaches, yet clinically accessible platforms for ex vivo pharmacological evaluation remain limited. This stud...
Effective inflammatory bowel disease (IBD) management increasingly relies on patient-stratified therapeutic approaches, yet clinically accessible platforms for ex vivo pharmacological evaluation remain limited. This study establishes patient-derived tissue slice cultures from routine endoscopic biopsies (ePDTC), as a potential translational platform for individualized drug response assessment. ePDTC were generated from routine colonic biopsies of ulcerative colitis (UC, N = 11), Crohn's disease (CD, N = 7), and non-IBD control patients (N = 3). Tissue slices (350 μm high) were cultured at an air-liquid interface for 24 and 48 h, assessed for viability, immune cell composition, transcription factor activation, and mediator release profiles. Pharmacological responsiveness was evaluated using budesonide (1 µM) and myrrh extracts (50-100 µg/mL). Structural integrity was preserved in 88.4% of ePDTC at 24 h after start of cultivation with low apoptosis rates (median: 1.21%), but declined to 56.0% of tissues at 48 h. ePDTC preserved disease-specific inflammatory signatures, including distinct neutrophil patterns between UC and CD subtypes. Budesonide significantly reduced 17 of 24 inflammatory mediators after 24 h (adjusted P < 0.001) with indication of disease subtype-specific response patterns in principal component analysis. Myrrh extracts demonstrated concentration-dependent responses. Biopsy-derived ePDTC provide a clinically accessible ex vivo platform that preserves native tissue complexity and demonstrates the capacity to capture inter-individual pharmacodynamic heterogeneity within a 24-hour experimental window. This provides a biological basis for future patient-stratified pharmacological evaluation.
Identification of circadian rhythm-associated key genes in metabolic dysfunction-associated fatty liver disease.
Luo J, Ma X, Wang Q … +5 more , Zhang R, Zhu L, Feng X, Wang W, Geng J
Clin Exp Med · 2026 Jun · PMID 42329455 · Publisher ↗
As of now, current studies have confirmed that circadian rhythm genes (CRGs) can modulate the onset and development of metabolic dysfunction-associated fatty liver disease (MAFLD). Leveraging computational biology method...
As of now, current studies have confirmed that circadian rhythm genes (CRGs) can modulate the onset and development of metabolic dysfunction-associated fatty liver disease (MAFLD). Leveraging computational biology methodologies, systematic and thorough investigations into MAFLD and CRGs enhance our capacity to gain deeper insights into the disease's pathogenic mechanisms. MAFLD-associated datasets (GSE89632 and GSE126848) and 248 circadian rhythm genes genes (CRGs) were analyzed. Principal component analysis (PCA) was performed on the GSE89632 dataset, and samples were divided into training and test sets. Differentially expressed genes (DEGs) from the training set were intersected with key module genes from WGCNA to identify intersection genes. These were then analyzed for expression consistency across datasets, followed by machine learning to identify key genes. Further analyses, including nomogram development, gene set enrichment analysis (GSEA), immune infiltration, and drug prediction, were also conducted. Four outliers were excluded, leaving 17 MAFLD and 22 control samples for analysis. 141 intersection genes were identified, with 36 showing consistent expression trends. Machine learning identified SOCS2, FBXO27, and HMMR as key genes. A nomogram based on these genes predicted MAFLD patient survival. GSEA revealed significant enrichment in pathways like olfactory transduction and peroxisome. Mast cell activation correlated strongly with SOCS2 and FBXO27. SOCS2, FBXO27, and HMMR are identified as key genes in MAFLD, providing new insights into the disease mechanisms.
No serological association between Porphyromonas gingivalis or Prevotella intermedia and early spondyloarthritis: analysis from the DESIR cohort.
Zekre F, Neel T, Paul M … +3 more , Normand M, Tournadre A, Marotte H
Clin Exp Med · 2026 Jun · PMID 42329427 · Publisher ↗
Porphyromonas gingivalis and Prevotella intermedia are key oral pathogens implicated in periodontal disease and have been associated with rheumatoid arthritis and specific categories of juvenile idiopathic arthritis. Whe...
Porphyromonas gingivalis and Prevotella intermedia are key oral pathogens implicated in periodontal disease and have been associated with rheumatoid arthritis and specific categories of juvenile idiopathic arthritis. Whether oral dysbiosis involving Porphyromonas gingivalis or Prevotella intermedia contributes to axial spondyloarthritis pathogenesis remains unclear. We evaluated Porphyromonas gingivalis- and Prevotella intermedia-specific IgG titres across early axial spondyloarthritis phenotypes within the DESIR cohort and assessed the potential influence of smoking status. Serum samples from 554 participants in the DESIR cohort were analyzed. Anti-Porphyromonas gingivalis and anti-Prevotella intermedia IgG titres were measured using a validated in-house enzyme-linked immunosorbent assay. Patients were classified into axial spondyloarthritis, axial spondyloarthritis with psoriasis, axial spondyloarthritis with inflammatory bowel disease, undifferentiated axial spondyloarthritis, or chronic low back pain controls. Antibody titres were compared using non-parametric tests. In addition, multivariable logistic and linear regression analyses were performed adjusting for age, sex, BMI and smoking status. Anti-Porphyromonas gingivalis and anti-Prevotella intermedia IgG titres did not differ significantly across axial spondyloarthritis phenotypes or between axial spondyloarthritis subgroups and chronic low back pain controls (Porphyromonas gingivalis: p = 0.622; Prevotella intermedia: p = 0.491). These findings remained unchanged after multivariable adjustment for age, sex, BMI, and smoking status (all p > 0.1). Smoking status did not influence serological patterns in any group. Distributional analyses confirmed strong overlap in antibody titres across all phenotypes, with no subgroup showing a distinct P. gingivalis or P. intermedia serological signature. In this large early axial spondyloarthritis cohort, antibody responses to Porphyromonas gingivalis and Prevotella intermedia did not differ across phenotypes and showed no detectable serological association with axSpA. These findings did not support a major role of Porphyromonas gingivalis - or Prevotella intermedia-related systemic humoral responses in early axial spondyloarthritis, although they did not exclude a broader role of mucosal dysbiosis in disease pathogenesis.
Development and validation of a multimodal machine learning prediction model for heart failure after acute myocardial infarction.
Wu X, Cui H, Wang S … +11 more , Zheng X, Hou X, Ran L, Liu J, Wang Z, Ren M, Yao J, Ma H, Zheng Y, Wu J, Yu B
Clin Exp Med · 2026 Jun · PMID 42329309 · Publisher ↗
Heart failure after acute myocardial infarction (post-MI HF) has become a major global health problem. Accurate risk prediction is essential for optimising management and preventing post-MI HF. However, existing models r...
Heart failure after acute myocardial infarction (post-MI HF) has become a major global health problem. Accurate risk prediction is essential for optimising management and preventing post-MI HF. However, existing models rely mainly on resting-state clinical examinations and inadequately reflect the complex pathophysiology of post-MI HF. We aimed to develop and validate a multimodal machine learning (ML) model incorporating cardiopulmonary exercise testing (CPET) data to predict post-MI HF risk and to quantify CPET's incremental value.This study included 3172 acute myocardial infarction (AMI) patients who underwent CPET at three hospitals from 2018 to 2023. The primary outcome was post-MI HF within 1 year. Thirteen ML algorithms were used to select clinical and CPET variables and to construct multimodal prediction models. The incremental predictive value of CPET was evaluated by the area under the curve (AUC), integrated discrimination improvement index (IDI), and net reclassification improvement index (NRI).After screening, 2221 patients were included, of whom 221 (10.0%) developed post-MI HF. The optimal multimodal ML model achieved an AUC of 0.987 (95% CI: 0.982-0.992) in training set and 0.929 (95% CI: 0.903-0.955) in external validation set. Ablation analyses showed that CPET significantly improved discrimination (AUC: 0.890 vs. 0.929, P=0.003), calibration (IDI=0.135 [95% CI: 0.082-0.189], P<0.001), and reclassification (NRI=0.154 [95% CI: 0.073-0.234], P<0.001). The model effectively stratified low- and high-risk patients (3.1% vs. 54.7%, P<0.001). The multimodal ML model accurately predicted post-MI HF and highlighted the additive value of CPET in risk stratification. The web-based risk calculator derived from this model may support early identification of high-risk patients and facilitate personalised management.
The oncogenic role, regulatory mechanism, and clinical significance of lncRNA HIF1A-AS2 in multiple human cancers.
Luo L, Zhang J, Yu T … +3 more , Tang W, Dong J, Yang F
Clin Exp Med · 2026 Jun · PMID 42323762 · Publisher ↗
Long non-coding RNAs (lncRNAs) are RNA molecules transcribed over 200 nucleotides in length. Although they do not encode proteins, many studies have shown that they have a dramatic involvement in human cancer by various...
Long non-coding RNAs (lncRNAs) are RNA molecules transcribed over 200 nucleotides in length. Although they do not encode proteins, many studies have shown that they have a dramatic involvement in human cancer by various mechanisms. Hypoxia inducible factor 1α-antisense RNA 2 (HIF1A-AS2) is a lncRNA recently described to map on human chromosome 14q23.2, whose aberrant expression has been observed in many tumor types and whose up-regulation results in poor patient clinical prognosis. Experimental studies demonstrate that HIF1A-AS2 is involved in a wide range of biological processes, including cell proliferation, invasion, migration, apoptosis, drug resistance and epithelial-mesenchymal transition (EMT). Moreover, this lncRNA promotes cancer malignancy by acting as competing endogenous RNA (ceRNA) or by directly binding to certain proteins. This article comprehensively summarizes the function, molecular mechanisms, and clinical significance of HIF1A-AS2 in malignant tumors, pointing out that HIF1A-AS2 has potential functions as diagnostic markers as well as therapeutic targets.
tRF-18-8R1546D2 is upregulated in hepatocellular carcinoma and associated with poor prognosis and tumor progression.
Yuan LX, Yue ZQ, Xiao JW … +5 more , Ju LL, Wang HX, Tan JJ, Xiao F, Chen L
Clin Exp Med · 2026 Jun · PMID 42323524 · Publisher ↗
This study aimed to investigate the clinical significance of tRF-18-8R1546D2 in hepatocellular carcinoma and to explore its potential role in tumor progression. tRF-18-8R1546D2 was identified as a potential oncogenic fac...
This study aimed to investigate the clinical significance of tRF-18-8R1546D2 in hepatocellular carcinoma and to explore its potential role in tumor progression. tRF-18-8R1546D2 was identified as a potential oncogenic factor in HCC based on PCR Array sequencing. Its expression levels and subcellular localization in HCC were examined using qRT-PCR, FISH, and nuclear-cytoplasmic RNA fractionation. ROC curve, Cox and survival analysis were performed to determine the diagnostic and prognostic value. EdU incorporation, colony formation, apoptosis and transwell assays were conducted to assess cellular functions of tRF-18-8R1546D2. KEGG and Go analysis were conducted to seek for possible pathways in HCC progression. Bioinformatics analysis was conducted to screen potential targets of tRF-18-8R1546D2. qRT-PCR and IHC were used to examine the ECM2 expression, and its association with tRF-18-8R1546D2 was examined using correlation, dual-luciferase reporter assays and rescue assays. tRF-18-8R1546D2 was upregulated in HCC tissues, cell lines and plasma, its high expression was associated with poor prognosis and early detection. Cox analysis confirmed that tRF-18-8R1546D2 was a clinically potential prognostic marker. Functional assays revealed that overexpression of tRF-18-8R1546D2 promoted cell proliferation, migration, invasion in HCC and reduced apoptosis, the knockdown of tRF-18-8R1546D2 yielded the opposite results. ECM2 was downregulated in HCC tissues and cell lines, shown a better prognostic value and enriched in EMT pathways. Finally, Bioinformatics analysis, correlation, dual-luciferase reporter assays and rescue assays shown that tRF-18-8R1546D2 may downregulate ECM2 expression. tRF-18-8R1546D2 plays an oncogenic role in HCC and may drive tumor progression through downregulation of ECM2. Importantly, tRF-18-8R1546D2 may assist HCC detection, prognosis and treatment.
Poor self-rated health is twice as common in rheumatoid arthritis: population-based evidence from the Paracelsus 10,000 study.
Ausserwinkler M, Bartsch V, Gensluckner S … +7 more , Paulweber B, Trinka E, Langthaler P, Iglseder B, Flamm M, Aigner E, Wernly B
Clin Exp Med · 2026 Jun · PMID 42322460 · Publisher ↗
Self-rated health (SRH) is a simple but powerful predictor of morbidity and mortality. Its relevance in rheumatoid arthritis (RA) has not been systematically investigated in population-based cohorts. We analyzed 9,399 pa...
Self-rated health (SRH) is a simple but powerful predictor of morbidity and mortality. Its relevance in rheumatoid arthritis (RA) has not been systematically investigated in population-based cohorts. We analyzed 9,399 participants of the Paracelsus 10,000 study, including 293 (3.1%) with physician-diagnosed RA. SRH was assessed with a single-item global question. Associations of RA, sociodemographic, metabolic, and lifestyle factors with poor SRH were examined using multivariable logistic regression. Poor or very poor SRH was reported by 55% of RA participants compared with 31% of non-RA participants (p < 0.001). RA was independently associated with more than twofold higher odds of poor SRH (adjusted OR 2.21 (95% CI 1.61-3.02). Advanced age, metabolic syndrome, and current smoking were linked to worse SRH, whereas male sex, higher education, and higher physical activity were protective. Each one-point increase in Mediterranean diet adherence (PREDIMED score) was associated with a 4% lower odds of poor SRH (OR 0.96, 95% CI 0.94-0.99). No interaction between RA and diet adherence was observed. RA is strongly associated with poor self-rated health in the general population, after adjustment for comorbidities and lifestyle factors. Higher adherence to the Mediterranean diet and greater physical activity were linked to better perceived health, highlighting modifiable targets to improve patient-centered outcomes in RA.
Retraction Note: Curcumin inhibits LPA-induced invasion by attenuating RhoA/ROCK/MMPs pathway in MCF7 breast cancer cells.
Sun K, Duan X, Cai H … +5 more , Liu X, Yang Y, Li M, Zhang X, Wang J
Clin Exp Med · 2026 Jun · PMID 42319569 · Full text
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Correction: Clinicopathological profile of basal cell carcinoma: a retrospective study from Limpopo province, South Africa.
Manenzhe R, McCusker CP, Mhlongo LN
Clin Exp Med · 2026 Jun · PMID 42319545 · Full text
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Decoding chromatin regulator-LAIR1 M2 like macrophage patterns in atherosclerosis and clinical outcomes of Lung adenocarcinoma patients: evidence from artificial intelligence-driven multi omics and in vitro validation.
Zhang C, Chen B, Li Z … +2 more , Li X, Jiang W
Clin Exp Med · 2026 Jun · PMID 42319401 · Publisher ↗
Atherosclerosis (AS) is a common complication of lung adenocarcinoma (LUAD), but its underlying mechanisms in LUAD remain unclear. This study aimed to decipher the role of chromatin regulators in AS pathogenesis and thei...
Atherosclerosis (AS) is a common complication of lung adenocarcinoma (LUAD), but its underlying mechanisms in LUAD remain unclear. This study aimed to decipher the role of chromatin regulators in AS pathogenesis and their association with clinical outcomes in LUAD patients. AS- and chromatin regulator (CR)-associated prognostic indicators were identified in LUAD and analyzed in the TCGA-LUAD cohort using Cox regression and Disease Ontology analysis. CR-related risk subgroups were defined by NMF in the GSE26939 cohort. GSVA and WGCNA, combined with interpretable machine learning, were used to construct a predictive model and identify key genes, which were validated in GSE68465. The molecular features of key genes and their roles in AS were further evaluated. Besides, mechanisms of key genes in M2-like macrophages were assessed at the single-cell level in LUAD patients using cutting-edge analytical frameworks. A deep learning framework and molecular docking were used to screen natural compounds. Finally, co-culture experiments were conducted for validation. CR signatures can guide the LUAD patients LUAD patients into high- and low-AS risk groups and were associated with clinical outcomes. LAIR1 can be considered as an AS-related factor enriched in M2-like macrophages and involved in LUAD progression. Quercetin was identified as potential preventive agent for AS in LUAD patients. CR-associated signatures play an important role in AS pathogenesis and LUAD progression.
Engineered small extracellular vesicles in hematologic malignancies: mechanisms, therapeutic strategies, and translational challenges.
Hsu CY, Murtazaev S, Zubair SH … +7 more , Abohassan M, Patel PN, Singh G, Arora V, Nayak PP, Iqbal MS, Abbas ZK
Clin Exp Med · 2026 Jun · PMID 42313192 · Publisher ↗
Hematologic malignancies remain among the most challenging cancers to treat due to genetic heterogeneity, clonal evolution, and therapy resistance. Extracellular vesicles (EVs), particularly small EV (sEV)-enriched popul...
Hematologic malignancies remain among the most challenging cancers to treat due to genetic heterogeneity, clonal evolution, and therapy resistance. Extracellular vesicles (EVs), particularly small EV (sEV)-enriched populations, have emerged as active mediators of disease biology, contributing to tumor progression, immune evasion, and chemoresistance through intercellular transfer of bioactive cargo. Recent advances in EV engineering have repositioned these vesicles as programmable delivery platforms capable of transporting nucleic acids, proteins, and chemotherapeutic agents with improved targeting potential. Preclinical studies across multiple hematologic models demonstrate that engineered EVs can induce immune activation, modulate oncogenic signaling pathways, and partially overcome drug resistance. However, these findings remain largely confined to experimental settings, with limited standardization of loading efficiency, biodistribution, and functional potency. Clinically, EV-based applications in hematology are still at an early stage, with most studies focused on biomarker discovery and supportive therapies rather than direct antitumor interventions. In parallel, theranostic EV platforms and liquid biopsy approaches offer promising opportunities for minimally invasive disease monitoring, although their clinical validation remains incomplete. Artificial intelligence (AI) further enhances this field by enabling advanced biomarker analysis and guiding cargo design and targeting strategies, yet its therapeutic applications are still largely exploratory. Despite key challenges, including vesicle heterogeneity, donor variability, suboptimal cargo loading, and manufacturing constraints, these limitations are primarily technical and may be addressed through standardization and engineering optimization. Collectively, EV-based systems represent a promising but still maturing platform with the potential to contribute to next-generation precision oncology in hematologic malignancies.
Zinc supplementation ameliorates colitis in mice by sensitizing pathogenic CD4 T cells to ferroptosis.
Li Z, Cai J
Clin Exp Med · 2026 Jun · PMID 42310170 · Publisher ↗
Inflammatory Bowel Disease (IBD) is driven by the hyperactivation of pathogenic Th1 and Th17 subsets. Although clinical zinc deficiency strongly correlates with severe IBD outcomes, the precise immunomodulatory mechanism...
Inflammatory Bowel Disease (IBD) is driven by the hyperactivation of pathogenic Th1 and Th17 subsets. Although clinical zinc deficiency strongly correlates with severe IBD outcomes, the precise immunomodulatory mechanisms underlying this association remain unknown. To systematically investigate the role of zinc in CD4 T cell fate determination and intestinal homeostasis, we evaluated its immunomodulatory dynamics using a murine colitis model alongside in vitro differentiation assays employing human primary naive CD4 T cells. We found that zinc supplementation remarkably ameliorated experimental mucosal damage by abruptly halting the local infiltration of pathogenic CD4 T cells. Both in vivo and in vitro analyses revealed that zinc does not merely stall T cell polarization, but actively sensitizes these effector subsets to cell demise. Comprehensive transcriptomic sequencing pinpointed the ferroptosis cascade as the critical mediator of this clearance mechanism. Specifically, zinc systematically suppressed T cell anti-ferroptotic defenses by downregulating GPX4 and SLC7A11, while concurrently amplifying pro-ferroptotic drivers such as ACSL4. This targeted metabolic stress profoundly sensitized hyperactive T cells to ferroptosis, effectively purging the inflammatory mucosal niche. Ultimately, these findings reframe the fundamental role of zinc in intestinal immune homeostasis, exposing ferroptosis as a druggable vulnerability in IBD and providing a strong mechanistic rationale for zinc-based clinical interventions.
IL10 promotes surgical incision healing in sepsis by regulating PI16 fibroblasts and CCL8 macrophages.
He X, Xu C, Zou Y … +3 more , Wang W, Wu L, Zhou Q
Clin Exp Med · 2026 Jun · PMID 42310159 · Publisher ↗
Sepsis severely impairs surgical incision healing, but the underlying mechanisms and effective interventions remain insufficiently understood. Interleukin-10 (IL10) exerts potent anti-inflammatory activity, yet its role...
Sepsis severely impairs surgical incision healing, but the underlying mechanisms and effective interventions remain insufficiently understood. Interleukin-10 (IL10) exerts potent anti-inflammatory activity, yet its role in regulating fibroblast and macrophage dynamics during septic wound repair is unclear. Human peri-incisional skin specimens were collected from septic and non-septic patients. A lipopolysaccharide (LPS)-induced sepsis mouse model with surgical incision was established, followed by IL10 treatment. Single-cell RNA sequencing, cell trajectory analysis, cell-cell communication analysis, gene set variation analysis, and immunofluorescence were used to investigate cellular and molecular alterations. Only mouse samples were used for single-cell sequencing in this study. Single-cell analysis identified 8 cell types, including 3 non-immune cell types and 5 immune cell types. Sepsis increased NK cells and macrophages, and upregulated PI16⁺ fibroblasts and CCL8⁺ macrophages in wound tissue. IL10 treatment elevated mast cells, T cells, and neutrophils, downregulated peptidase inhibitor 16 (Pi16) and chemokine ligand 8 (Ccl8) expression, and attenuated fibroblast-macrophage crosstalk. Mechanistically, IL10 promoted fibroblast proliferation by inducing macrophages to secrete Il1b and Osm. Sepsis delays surgical incision healing via upregulating PI16⁺ fibroblasts and CCL8⁺ macrophages and enhancing inflammatory cell crosstalk. IL10 accelerates wound repair by suppressing these detrimental subsets and activating Il1b/Osm-mediated fibroblast proliferation. PI16 and CCL8 may serve as potential therapeutic targets for septic wound healing.
Absence of osteoclastogenic response to pooled polyclonal anti-citrullinated peptide/protein antibodies from patients with rheumatoid arthritis in vitro.
Chen X, An Z, Li C … +1 more , Zhao J
Clin Exp Med · 2026 Jun · PMID 42307680 · Publisher ↗
Anti-citrullinated peptide/protein antibodies (ACPAs) are specific serological markers for rheumatoid arthritis (RA), but their direct role in promoting osteoclastogenesis remains controversial. This study aims to determ...
Anti-citrullinated peptide/protein antibodies (ACPAs) are specific serological markers for rheumatoid arthritis (RA), but their direct role in promoting osteoclastogenesis remains controversial. This study aims to determine whether polyclonal ACPAs purified from RA patients can directly drive osteoclastogenesis in vitro. Polyclonal ACPAs were purified from pooled sera of 37 ACPA positive RA patients using Protein G and multi-citrullinated-epitope peptide (MCEP) conjugated affinity chromatography, with control IgG from 10 ACPA negative RA patients and a healthy donor. The purity and specific binding capability to citrullinated vimentin were verified by Coomassie Blue staining and western blot. CD14 + monocytes from healthy donors and RA patients were induced to differentiate into osteoclasts with M-CSF and RANKL, in the presence or absence of ACPAs. Osteoclast formation was evaluated by tartrate resistant acid phosphatase (TRAP) staining, gene expression of osteoclast-specific markers (TRAP, cathepsin K, MMP9) by quantitative PCR, and bone resorption activity by scanning electron microscopy. The purified ACPAs showed intact IgG structure of heavy and light chains, and specific binding to citrullinated vimentin, but not to native vimentin. However, ACPAs treatment did not significantly increase the number of TRAP-positive multinucleated cells, the expression of osteoclast-related genes, or bone resorption pit area compared to controls. Our findings demonstrate that pooled polyclonal ACPAs from RA patients, purified by MCEP affinity chromatography, do not directly promote osteoclastogenesis in vitro, suggesting that their osteoclastogenic effects may require a more complex microenvironment or depend on specific antibody properties not captured in this experimental setting.
PYCR1 promotes glutamine metabolism and the progression of lung adenocarcinoma by regulating the expression of OPLAH.
Chen W, Wang K, Wang R … +4 more , Deng X, Liu X, Dai P, Liu Q
Clin Exp Med · 2026 Jun · PMID 42295575 · Publisher ↗
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Glutamine plays a critical role in the progression of LUAD. However, the function of pyrroline-5-carboxylate reductase 1 (PYCR1) and its regulatory ro...
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Glutamine plays a critical role in the progression of LUAD. However, the function of pyrroline-5-carboxylate reductase 1 (PYCR1) and its regulatory role in glutamine metabolism remain unclear. Transcriptomic and clinical data for LUAD were obtained from The Cancer Genome Atlas (TCGA) and validated using Gene Expression Omnibus (GEO) datasets (GSE19188, GSE13213). Glutamine metabolism-related genes were analyzed for differential expression and prognostic significance. Functional enrichment was performed via gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses. Single-cell RNA-seq data (GSE117570) were processed using Seurat, and cell-cell communication was inferred with CellChat. In vitro, lentiviral overexpression, Western blotting, EdU, CCK-8, and glutamine uptake assays were conducted. An orthotopic xenograft model was established in nude mice to assess tumor growth in vivo. Six glutamine-metabolism-related genes were found significantly overexpressed in LUAD tissues and associated with poor overall survival. Single-cell sequencing revealed predominant PYCR1 expression in malignant cells. Functional assays demonstrated that PYCR1 overexpression enhanced glutamine uptake, proliferation, and inhibited apoptosis in LUAD cells, effects mediated via suppression of the P53 pathway. PYCR1 promoted tumor growth in a xenograft model and was found to transcriptionally upregulate 5-oxoprolinase (OPLAH), which augmented its oncogenic effects. Our findings identify the PYCR1/OPLAH axis as a key driver of LUAD progression via p53 signaling, revealing a promising therapeutic target.
ALKBH2 promotes the Warburg effect and bladder cancer progression under hypoxic conditions via the PI3K/AKT pathway.
Yang Z, Ma J, Qiang Z … +8 more , Xie W, Jiao L, Hu Z, Zhang T, Zhang L, Lv J, Yue F, Chen G
Clin Exp Med · 2026 Jun · PMID 42295564 · Publisher ↗
Emerging evidence links DNA repair enzymes to metabolic reprogramming in cancer. ALKBH2 safeguards genomic integrity by reversing alkylation damage, yet its potential role beyond repair-specifically in modulating the War...
Emerging evidence links DNA repair enzymes to metabolic reprogramming in cancer. ALKBH2 safeguards genomic integrity by reversing alkylation damage, yet its potential role beyond repair-specifically in modulating the Warburg effect-remains unexplored in bladder cancer. While implicated in digestive tract malignancies, ALKBH2's function in urothelial carcinoma is unknown. Investigating this gap may reveal ALKBH2 as a novel metabolic driver in bladder cancer progression. ALKBH2 expression was analyzed in bladder cancer tissues and matched adjacent normal tissues by qPCR, Western blotting, and immunofluorescence (IF). Hematoxylin and eosin (H&E) staining was used to confirm tissue histology. Using stable ALKBH2-overexpressing and knockdown bladder cancer cell lines, we systematically assessed the effects of ALKBH2 on tumor cell behavior in vitro and tumor growth in vivo. Moreover, its involvement in hypoxia-associated Warburg metabolic reprogramming was investigated under 1% O₂. In vitro, ALKBH2 overexpression enhanced bladder cancer cell proliferation, migration, invasion, and clonogenicity, whereas ALKBH2 knockdown exerted opposite effects. Consistently, in vivo xenograft models demonstrated that silencing ALKBH2 significantly suppressed tumor growth. Mechanistic investigations revealed that ALKBH2 functions as an m6A demethylase to reduce PTEN mRNA stability, thereby activates the PI3K/AKT signaling pathway under hypoxic conditions, as evidenced by increased pathway activation, thereby facilitating metabolic reprogramming and tumor cell progression. These findings suggest that ALKBH2 plays a critical oncogenic role in bladder cancer by regulating PI3K/AKT pathway activation and promoting the Warburg effect, highlighting its potential as a therapeutic target for bladder cancer.
Dissecting PCD-driven molecular landscapes in AML: a multi-omic framework for prognostication and therapeutic targeting.
Liu J, Zhong F, Wang X … +5 more , Xu L, Tu Z, Cheng X, Zhang L, Kong G
Clin Exp Med · 2026 Jun · PMID 42295454 · Publisher ↗
Acute myeloid leukemia (AML) remains a molecularly heterogeneous malignancy with poor prognosis, necessitating robust biomarkers for risk stratification. By integrating single-cell RNA-seq and multiomics data from 2,680...
Acute myeloid leukemia (AML) remains a molecularly heterogeneous malignancy with poor prognosis, necessitating robust biomarkers for risk stratification. By integrating single-cell RNA-seq and multiomics data from 2,680 AML samples across 10 cohorts, we demonstrate that dysregulated programmed cell death (PCD) pathways are significantly elevated in AML cells and correlate with adverse outcomes. Unsupervised clustering identified two PCD-driven subtypes: Subtype A exhibits high PCD activity, an immunosuppressive microenvironment (M2 macrophages, upregulated PD-L1/HAVCR2), increased somatic mutations (NPM1/DNMT3A/FLT3), and poor survival, while Subtype B shows lower PCD activity, immune-active features, and better prognosis. As an exploratory analysis, subtype-specific therapeutic vulnerabilities were revealed: Subtype A displays predicted sensitivity to immune checkpoint inhibitors (anti-PD-1) and tipifarnib, whereas Subtype B responds better to cytarabine/doxorubicin. We developed PCDRScore-a prognostic model incorporating 13 PCD-related genes via machine learning-which outperformed existing models (higher C-index) in 10 validation cohorts and remained independent of clinicopathological factors. A nomogram combining PCDRScore, age, and cytogenetic risk enhanced clinical applicability. Crucially, experimental validation confirmed significant upregulation of key model genes (HIP1, SQLE, VNN1) in AML patient samples and cell lines (P < 0.05), reinforcing the model's biological relevance. These findings establish PCD dysregulation as a central axis of AML heterogeneity, providing a framework for precision risk stratification and hypothesis-generating immunophenotype-guided therapy.
Identifying PLAU as a shared pathogenic gene in type 2 diabetes and bladder urothelial carcinoma through integrated transcriptomic analysis and machine learning for diagnostic and therapeutic value.
Xin S, Li G, Yang X … +9 more , Su J, Li R, Qin W, Zhang Z, Wang C, Zhu Y, Feng L, Ren S, Gao Z
Clin Exp Med · 2026 Jun · PMID 42268472 · Publisher ↗
Type 2 diabetes mellitus (T2DM) and bladder urothelial carcinoma (BLCA) are two kinds of diseases that seriously threaten human health. Their pathogenesis is complex and involves the interaction of multiple genes and mul...
Type 2 diabetes mellitus (T2DM) and bladder urothelial carcinoma (BLCA) are two kinds of diseases that seriously threaten human health. Their pathogenesis is complex and involves the interaction of multiple genes and multiple pathways. Recent epidemiological studies have shown that the risk of BLCA in patients with T2DM is significantly higher than that in non-diabetic people, suggesting that there may be a potential biological correlation between the two. Genomic studies have opened up new ways to reveal the common genetic characteristics of T2DM and BLCA. However, most of the current studies only focus on a single disease, and the comorbidity mechanism of these two diseases still needs to be further explored. Firstly, the datasets of BLCA and T2DM were downloaded from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases respectively. Differential expression genes (DEGs) were identified using the Limma package. Weighted gene co-expression network analysis (WGCNA) was employed to determine the co-expression modules related to BLCA and T2DM, and the common potential target genes were obtained. Correlation analysis and enrichment analysis were conducted on these target genes. Then, the best diagnostic biomarker - plasminogen activator (PLAU) was selected using machine learning algorithms. Additionally, the role of PLAU in the progression of T2DM and BLCA was confirmed through immunohistochemistry, Western Blot, and Edu experiments. Finally, small molecule compounds targeting PLAU were discovered through molecular docking and virtual screening, and the inhibitory effect of these small molecules on the progression of bladder urothelial carcinoma was verified through experiments. This study conducted a combined limma and WGCNA analysis on the T2DM and BLCA datasets to identify 42 common potential target genes, which were enriched in pathways such as innate immunity. Using machine learning algorithms such as LASSO and SVM, PLAU was identified as the best diagnostic marker for T2DM combined with BLCA. It was significantly highly expressed in both T2DM and BLCA samples, and high expression of PLAU predicted a shorter overall survival period for BLCA patients. Experimental results confirmed that PLAU was highly expressed in BLCA tissues and increased with the severity of malignancy. Knockdown (sh-PLAU) of PLAU could inhibit cancer cell proliferation and migration in a high-glucose environment, while overexpression (oe-PLAU) still promoted cancer cell progression in a low-glucose environment. Finally, molecular docking virtual screening revealed that the small molecule compound epigallocatechin gallate (EGCG) could target and inhibit PLAU, and effectively inhibited the proliferation and invasion of BLCA cells in experiments. The results of this study reveal the role of PLAU, a common characteristic gene of T2DM and BLCA, whose high expression drives tumor progression and poor prognosis. Moreover, small molecule drugs targeting PLAU, such as EGCG, have therapeutic potential. This study provides a new direction for accurate diagnosis and treatment of BLCA patients with T2DM.
Thromboembolic risk in subcutaneous versus intravenous immunoglobulin therapy: a systematic review and narrative meta-synthesis.
Fang S, Chen YC, Chen S
Clin Exp Med · 2026 Jun · PMID 42268448 · Publisher ↗
Intravenous immunoglobulin (IVIg) therapy is associated with thromboembolic complications, including deep vein thrombosis (DVT), pulmonary embolism (PE), ischaemic stroke, and myocardial infarction (MI). Subcutaneous imm...
Intravenous immunoglobulin (IVIg) therapy is associated with thromboembolic complications, including deep vein thrombosis (DVT), pulmonary embolism (PE), ischaemic stroke, and myocardial infarction (MI). Subcutaneous immunoglobulin (SCIg) achieves lower peak serum IgG concentrations and may confer a reduced thromboembolic risk. We systematically reviewed the comparative thromboembolic safety of SCIg versus IVIg across neurological and immunological indications. We searched PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov from inception to December 2024. Studies reporting thromboembolic events in patients receiving IVIg or SCIg for any indication were eligible. Two reviewers independently screened, extracted data, and assessed risk of bias. Where feasible, pooled incidence rates with 95% confidence intervals (CIs) were calculated using Freeman-Tukey double arcsine transformation. Thirty-four studies (approximately 12,800 patient-years of immunoglobulin exposure) were included. IVIg-treated patients (approximately 10,600 patient-years across 27 studies) experienced thromboembolic events at a pooled incidence of 1.8 per 100 patient-years (95% CI: 0.9-3.1). SCIg-treated patients (approximately 2,200 patient-years across 7 studies) had a pooled incidence of 0.14 per 100 patient-years (95% CI: 0.01-0.52). Only 3 thromboembolic events were documented in SCIg cohorts, all in patients with pre-existing prothrombotic risk factors. No head-to-head randomised trial comparing thromboembolic outcomes between routes exists. GRADE certainty was very low for the comparative estimate. Indirect evidence suggests that SCIg may be associated with a lower thromboembolic risk than IVIg, consistent with pharmacokinetic predictions. However, substantial differences in patient populations, follow-up duration, and event ascertainment between SCIg and IVIg cohorts preclude definitive conclusions. Prospective comparative trials with pre-specified thromboembolic endpoints are needed.
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