Wiley: Journal of Cellular and Molecular Medicine: Table of Contents

RNA Metabolism Genes as Prognostic Biomarkers and Therapeutic Targets in Colorectal Cancer Based on the Analysis of Single‐Cell and Bulk‐RNA Sequencing Data

Wed, 10 Jun 2026 20:59:59 -0700

ABSTRACT

Colorectal cancer (CRC) is one of the most common malignancies worldwide and remains a major cause of cancer-related mortality. Increasing evidence suggests that aberrant RNA metabolism contributes to tumour initiation, progression and therapeutic resistance. In this study, we integrated single-cell RNA sequencing and bulk transcriptomic data to identify RNA metabolism-related genes (RMRGs) associated with CRC progression and evaluate their clinical significance. Through comprehensive bioinformatics analyses, 39 differentially expressed RMRGs were identified, with high RMRG activity predominantly enriched in epithelial cell populations. Cell–cell communication analysis revealed enhanced interactions between epithelial cells and other cell types within the tumour microenvironment. Further integration of single-cell and bulk RNA-sequencing datasets identified PCBP3 and NGRN as key prognostic genes. A two-gene prognostic model based on PCBP3 and NGRN was established and validated in independent cohorts, demonstrating favourable predictive performance. Human Protein Atlas data further confirmed the expression of both proteins in colorectal cancer tissues. Immune infiltration analyses indicated that PCBP3 and NGRN were associated with distinct immune-cell infiltration patterns and immunotherapy-related immune status. Functional experiments demonstrated that silencing PCBP3 or NGRN significantly inhibited the proliferation and invasion of HCT116 colorectal cancer cells. Moreover, Western blot analysis suggested that these effects may be mediated, at least in part, through regulation of the PI3K/AKT signalling pathway. Collectively, our findings identify PCBP3 and NGRN as promising prognostic biomarkers and potential therapeutic targets in colorectal cancer and provide new insights into the role of RNA metabolism in colorectal cancer progression and tumour immune regulation.

Therapeutic Potential of Cucurbitacin I in Colon Adenocarcinoma Is Mediated by Modulation of SDHA Expression

Tue, 09 Jun 2026 20:55:43 -0700

ABSTRACT

Colorectal cancer is a prevalent malignancy, with colon adenocarcinoma (COAD) representing its most common histological subtype. Although most stage I patients remain disease-free after treatment, a subset rapidly progresses to advanced disease with markedly reduced survival. Therefore, identifying early molecular warning signals in stage I patients is essential for timely intervention. In this study, integrated datasets from The Cancer Genome Atlas and Genotype-Tissue Expression projects were analysed using the landscape dynamic network biomarker (l-DNB) approach to identify progression biomarkers (PBs) for COAD. Twenty PBs were identified, among which succinate dehydrogenase complex flavoprotein subunit A (SDHA) was selected for further investigation. The L1000CDS² database was subsequently queried utilizing these identified PBs, identifying Cucurbitacin I (CuI) as a promising therapeutic component against COAD. Molecular docking and molecular dynamics simulations demonstrated stable binding between CuI and SDHA, with a binding energy of −9.44 kcal/mol and an RMSD of 2.0 ± 0.3 Å. Subsequent in vitro experiments demonstrated that CuI treatment upregulated SDHA expression and inhibited activation of the NF-κB pathway. Collectively, these findings suggest that the identified PBs may serve as early-warning indicators for stage I COAD patients and that CuI suppresses COAD cell proliferation, potentially through the SDHA/NF-κB axis, highlighting its promise as a potential therapeutic candidate.

Potential Relationship Between YTHDF3 and CFTR in Myocardial Ischemia–Reperfusion Injury

Baoxin Tang, Chenying Zhu, Heqing Wang, Mingkui Gao, Tieyan Li — Tue, 09 Jun 2026 20:53:36 -0700

ABSTRACT

Myocardial ischemia–reperfusion injury (MIRI) is a common pathophysiological process in reperfusion therapy following myocardial infarction. It exacerbates myocardial damage and negatively impacts patient prognosis. This study aims to explore potential regulatory targets and related mechanisms in MIRI. Using the GSE123342 dataset, differentially expressed genes (DEGs) related to myocardial infarction-associated conditions were screened and a protein–protein interaction network was constructed. Core genes were identified through weighted gene co-expression network analysis (WGCNA), followed by GO and KEGG enrichment analyses. The GSE6381 dataset was used to examine core gene expression, and ROC curve analysis was performed as an exploratory assessment of group separation. A transcription factor regulatory network for CFTR was constructed using the KnockTF database. An oxygen–glucose deprivation/reoxygenation (OGD/OGR) model was established in AC16 cells, and plasmid overexpression of YTHDF3 and CFTR was used to examine their effects on OGD/OGR-induced cell injury. The interaction between YTHDF3 and CFTR mRNA was examined by RIP-qPCR experiments, and CFTR mRNA stability was assessed using an actinomycin D assay. Additionally, the effects of YTHDF3 and CFTR overexpression were examined in a rat I/R model. We found in the GSE123342 dataset, 5444 differentially expressed mRNAs were identified, with CFTR significantly upregulated. Correlation analysis revealed 6651 genes related to CFTR. WGCNA identified 120 hub genes, with the MEyellow module significantly associated with MIRI. These genes were mainly enriched in ABC transporters and the AMPK pathway. In the GSE6381 dataset, CFTR and YTHDF3 showed differential expression and ROC analysis showed preliminary group separation. CFTR was closely related to multiple transcription factors, including TP53, STAT3 and TFAP4. In AC16 cells, OGD/OGR decreased YTHDF3 expression and increased CFTR expression. YTHDF3 overexpression reduced CFTR expression and aggravated OGD/OGR-induced injury, as shown by reduced cell viability and proliferation and increased apoptosis. Additional CFTR overexpression partly attenuated these changes. In the rat I/R model, YTHDF3 overexpression increased myocardial infarct size and impaired cardiac function, whereas CFTR overexpression attenuated the injury associated with YTHDF3 overexpression. CFTR knockdown aggravated OGD/OGR-induced cellular injury and was associated with changes in AMPK signalling. Together, these findings suggest that YTHDF3 may be associated with MIRI and CFTR-related changes. Changes in AMPK signalling were also observed, but the underlying mechanism still needs further validation. These results provide preliminary evidence for a possible relationship between YTHDF3 and CFTR in MIRI.

The Impact of Airway Oxidative Stress on Macrophage Polarization in Stable Asthma and COPD: Association With Clinical Features in a Prospective Observational Study

Mon, 08 Jun 2026 21:49:32 -0700

ABSTRACT

The polarization status of pulmonary macrophages is dependent on cytokines and mediators present locally in the airways. This study aimed to evaluate whether oxidative stress present in the airways of asthma or COPD patients promotes M1 or M2 macrophage polarization. M1 macrophages predominated in COPD, whereas no increase in M2 macrophages was observed in any of the investigated groups. The elevated number of M1 in COPD was related to a higher level of increased oxidative stress marker mRNA expression, CYP1B1, and enhanced IL-6 and IL-8 levels. The M2 macrophage polarization was not disease-related and correlated with higher FEV₁/VC. Airway oxidative stress is related to M1 macrophage polarization in COPD, associated with increased inflammation and CYP1B1 mRNA expression. M1 macrophages were not related to clinical features in stable asthma or COPD, whereas higher levels of M2 macrophages were associated with better spirometry results.

β, β‐Dimethylacrylshikonin Triggers Caspase‐Mediated Cell Apoptosis via Heme Oxygenase‐1 Upregulation and ERK/p38 Activation in Prostate Cancer

Mon, 08 Jun 2026 21:46:39 -0700

ABSTRACT

β, β-Dimethylacrylshikonin (DMAS), a natural naphthoquinone derivative isolated from the root of a biennial herb belonging to the family Boraginaceae, has been demonstrated to exhibit anti-cancer and anti-inflammatory features. Yet, the effects of DMAS on restraining the progression of prostate cancer (PC) remain mostly elusive. Here, we attempted to examine whether DMAS hampers PC progression and subsequently explored the underlying mechanisms. Our results demonstrate that DMAS elicited cytotoxicity to PC cell lines, DU-145 and PC-3 cells, along with promotion of apoptosis and cell cycle arrest. Moreover, fluctuations in the levels of many potential apoptosis markers (upregulation of HO-1 and downregulation of cIAP-1 and XIAP) and activation of caspase pathways were observed in DMAS-treated PC cell lines. Furthermore, DMAS-induced caspase activations in PC cells were affected by silencing of HO-1 and the pretreatment with a selective ERK (U0126) or p38 inhibitor (SB203580), unveiling a functional linkage of HO-1, ERK, and p38 signalling to the responses of DMAS-treated PC cells. In conclusion, our results revealed that DMAS induced activation of caspase cascades to elicit cell apoptosis in PC, through HO-1 upregulation and ERK/p38 activation. These findings provide possible avenues for the use of a naturally occurring compound with therapeutic values in fighting prostate carcinogenesis.

Deferoxamine Improves Radiation‐Induced Peripheral Neuropathy

Sun, 07 Jun 2026 21:32:15 -0700

ABSTRACT

Radiation-induced peripheral neuropathy (RIPN) is a devastating sequela of radiation therapy (XRT). Current treatment options are limited. Deferoxamine (DFO) has been useful in treating radiation-induced dermal fibrosis. This study aimed to evaluate DFO for RIPN. Thus, 18 mice received 30Gy of fractionated XRT. After a fibrosis development interval, mice were treated with DFO injections, saline injections (Saline) or none (IR) (n = 6 per group). Longitudinal measures included footprint analysis, cold allodynia testing and monofilament testing. Immunofluorescent staining for myelination (MPZ) and axonal regeneration (GAP43) took place at the conclusion of the experiment. DFO improved motor deficits (Combined Toe Spread scores: −9.72, −12.91, −12.72 for DFO, Saline and IR, respectively). Additionally, DFO improved cold allodynia (duration ratios: 0.90, 0.70 and 0.73 for DFO, Saline and IR, respectively). Monofilament testing revealed the same trend, though not statistically significant. Additionally, DFO increased remyelination on MPZ staining (normalized myelin ratios: 0.84 DFO, 0.74 Saline, 0.72 IR) and increased axonal regeneration on GAP43 staining compared to all groups (pixel area: 3.76% DFO, 1.95% Saline, 1.94% IR, 2.09% Control). In conclusion, this murine study revealed DFO improves RIPN sensorimotor function. This is encouraging as disease-modifying treatments are limited for patients suffering from this XRT side effect.

Superoxide Dismutase–Centered Modulation by Curcumin in Cardiovascular Diseases: Mechanistic Insights and Translational Implications

Sun, 07 Jun 2026 21:31:07 -0700

ABSTRACT

Cardiovascular diseases (CVD) remain the leading global cause of morbidity and mortality, driven in part by dysregulated redox homeostasis and chronic inflammation. Superoxide dismutase (SOD), a key enzymatic defence against reactive oxygen species (ROS), plays a central role in maintaining cardiovascular integrity through regulation of oxidative stress across cytosolic (SOD1), mitochondrial (SOD2) and extracellular (SOD3) compartments. Impairment of SOD function contributes directly to endothelial dysfunction, myocardial injury and vascular remodelling. Curcumin (Cur), a pleiotropic polyphenol derived from Curcuma longa, has emerged as a potent modulator of SOD activity and expression. Evidence from preclinical models consistently demonstrates that Cur enhances SOD-dependent antioxidant defences, thereby attenuating oxidative damage, inflammation, apoptosis and fibrosis across multiple CVD contexts, including myocardial infarction, cardiomyopathy, hypertension and diabetic complications. While Cur also influences additional signalling pathways, such as NF-κB, PI3K/AKT and Nrf2, these effects are increasingly understood to converge on SOD-mediated redox regulation. Recent advances in nanodelivery systems have further improved Cur bioavailability and its capacity to modulate SOD activity in vivo. However, despite robust preclinical evidence, clinical validation remains limited. This review synthesizes current mechanistic and translational evidence, positioning SOD as the central mediator of Cur's cardioprotective effects and highlights key gaps in clinical translation.

Decoding the Oncogenic Role of GNG10 in Colorectal Cancer: A Non‐Canonical Wnt Pathway–Driven Mechanism

Sun, 07 Jun 2026 21:30:02 -0700

ABSTRACT

Guanine nucleotide-binding protein gamma 10 (GNG10) is implicated in various biological processes, yet its specific oncogenic role in colorectal cancer (CRC) remains poorly defined. This study aimed to elucidate the expression patterns, biological functions, and underlying mechanisms of GNG10 in CRC progression. We integrated TCGA datasets with tissue microarray immunohistochemistry and multivariate Cox regression models to evaluate the clinical significance of GNG10. Functional impacts on CRC malignant phenotypes and cancer stemness were assessed through gain- and loss-of-function models in vitro and in vivo. Mechanistic insights were gained via GSEA, Western blotting, and dual rescue strategies employing both pharmacological inhibition (Box5) and genetic depletion (shRHOA). We found that GNG10 was markedly overexpressed in CRC tissues, correlating with advanced pathological stage and poor overall survival. Multivariate analysis indicated that the prognostic value of GNG10 is closely associated with tumour progression. Functionally, GNG10 knockdown inhibited CRC cell proliferation, migration, and stemness while promoting apoptosis. Mechanistically, GNG10 activated the non-canonical Wnt/RHOA/JNK/NFATc1 signalling axis. Crucially, manipulation of GNG10 did not affect active or total β-catenin levels, thereby excluding canonical Wnt involvement. Both pharmacological inhibition with Box5 and genetic ablation of RHOA effectively abrogated GNG10-induced oncogenic phenotypes and the upregulation of cancer stem cell markers (CD44, CD133, OCT4, Nanog, SOX2). In vivo xenograft models confirmed that GNG10 knockdown suppressed tumour growth and decreased the expression of proliferation and stemness markers. Our findings demonstrate that GNG10 promotes CRC progression and stemness via the non-canonical Wnt signalling pathway. These findings highlight GNG10 as a promising prognostic indicator and a vulnerable target in CRC.

The NF‐κB Signalling Pathway: Mechanisms, Consequences and Therapeutic Targets

Bherouz Pourdad, Arash Pourdad — Thu, 04 Jun 2026 21:10:58 -0700

ABSTRACT

Nuclear Factor-kappa B (NF-κB) is a master transcriptional regulator orchestrating critical cellular processes, predominantly immunity and inflammation. However, its aberrant constitutive activation has emerged as a unifying pathogenetic hallmark across diverse malignancies, autoimmune disorders, and chronic inflammatory diseases. While the fundamental biology of canonical and non-canonical NF-κB signalling is well-established, translating this extensive knowledge into clinically viable therapeutics remains severely hindered by dose-limiting systemic toxicities and complex pharmacokinetic liabilities. This review critically evaluates the transition of NF-κB from a basic biological paradigm to a highly challenging yet promising therapeutic target. After a streamlined synthesis of its signalling dynamics and pathological implications across various disease states, the core focus of this report shifts to an in-depth analysis of next-generation therapeutic interventions. We specifically dissect advanced molecular strategies, moving beyond conventional pharmacological inhibitors to emphasize nucleic acid-based therapies, including decoy oligodeoxynucleotides (ODNs), peptide nucleic acids (PNAs), and locked nucleic acids (LNAs). Furthermore, we critically address current translational bottlenecks, highlighting the pivotal role of lipid nanoparticle (LNP) transporters and smart drug delivery systems in overcoming off-target effects. By mapping these cutting-edge modalities, this review underscores the critical necessity of transitioning from broad-spectrum inhibition toward context-specific, precision-engineered modulation of the NF-κB axis.

AFP Stimulates Glucose Metabolic Reprogramming Contributing to Hepatocellular Carcinoma Resist Sorafenib Through Activating PI3K/AKT Signalling Pathway

Thu, 04 Jun 2026 21:10:13 -0700

ABSTRACT

Alpha fetoprotein (AFP) regulates glucose metabolism reprogramming (GMR) related to drug resistance of hepatocellular carcinoma (HCC) and remains unclear. This study explores the effect of AFP regulating GMR (Glucose metabolic reprogramming) on the tolerance of HCC cells to sorafenib. Thirty clinical liver cancer samples and multi-omics databases were collected; the expression of AFP, GMR-related proteins, pyruvate kinase M2 (PKM2), and the PI3K/AKT signalling pathway-associated proteins were assessed using immunohistochemistry (IHC) or Western blotting. MTT, cloning assays, flow cytometry, and TUNEL were performed to evaluate the effects of AFP on HCC resistance to sorafenib. Alterations in glucose consumption, lactate dehydrogenase activity, and ATP production were measured. Co-immunoprecipitation and immunofluorescence experiments were conducted to determine how AFP interacts with PKM2. An in vivo mouse tumour model was used to investigate the restoration of tumorigenesis and development. The results indicated that AFP inhibited sorafenib-induced apoptosis of HCC cells. AFP activated the PI3K/AKT signalling pathway to promote the GMR-related protein expression and enzyme activity. Particularly, AFP's interaction with PKM2 stimulated the activity of PKM2 to enhance GMR, contributing to HCC resistance to sorafenib. In vivo experiments demonstrated that inhibition of AFP expression attenuated tumorigenesis and growth, and this effect was restored by overexpression of PKM2; PKM2 played a critical activated role in AFP mediating the GMR in HCC. In conclusion, AFP activates the PI3K/AKT signalling pathway to augment aerobic glycolysis in HCC cells, leading to HCC resistance to sorafenib. Inhibition of AFP expression and targeting of PKM2 may represent a novel approach for clinically reversing sorafenib tolerance in HCC patients.

GGAs: Regulation of Multiple Sorting Pathways and Potential Association With Human Diseases

Qinqin Wang, Juan Mei, Shuyue Li, Guoan Zhang, Jian Qiu, Xuezhi Li — Wed, 03 Jun 2026 21:15:13 -0700

ABSTRACT

Golgi-localized gamma-ear-containing Arf-binding proteins (GGAs) are a family of monomeric clathrin adaptors that function in intracellular vesicle trafficking. The three GGA family members—GGA1, GGA2 and GGA3—were first identified as sorting adaptors almost simultaneously by independent research groups in 2000. It is now well established that GGAs exert broad functions in intracellular sorting pathways. Moreover, GGAs have been shown to participate in diverse cellular processes including cell survival, migration and invasion, and are proposed to be potentially associated with multiple human disorders, such as Alzheimer's disease, cancers and type 2 diabetes mellitus. In this review, we briefly summarize the current knowledge regarding the roles of GGAs in intracellular vesicle trafficking, discuss the regulatory mechanisms underlying their functions, and speculate on their potential implications in human diseases. These findings may help us understand how GGAs participate in the pathogenesis of human diseases and, in the future, how to intervention the diseases via GGA-targeted strategies.

Elucidating the Mechanism of Oridonin in Treating Hepatocellular Carcinoma: Network Pharmacology and Experimental Validation

Wed, 03 Jun 2026 05:07:13 -0700

ABSTRACT

Oridonin, a bioactive diterpenoid derived from Rabdosia rubescens, has significant anti-tumour activity. Although previous studies have shown that oridonin has anti-liver cancer potential, the molecular mechanism of its treatment of hepatocellular carcinoma (HCC) still needs to be further investigated. This study utilized network pharmacology, molecular docking, and molecular dynamics simulations (MDS) to elucidate the mechanisms by which oridonin exerts its therapeutic effects on HCC. The findings were then validated by in vitro experiments. Initially, potential targets of oridonin for HCC were identified through online database retrieval. The mechanisms of oridonin in resisting HCC were then elucidated via integrated protein–protein interaction (PPI) network analysis, GO and KEGG enrichment analysis. Subsequently, these findings were confirmed through molecular docking, MDS and the in vitro experiments. A total of 273 intersecting targets were identified. Subsequently, PPI network analysis was performed, leading to the identification of 10 core targets. Molecular docking studies between these targets and oridonin suggested that PIK3R1, EGFR, AKT1, and JAK2 might be key targets. Further MDS demonstrated a strong interaction between oridonin and these key targets. Subsequent in vitro experiments revealed that oridonin significantly affects the cell cycle and induces apoptosis in HCC cells. Furthermore, oridonin significantly inhibits the expression of key targets within the EGFR/PI3K/AKT signalling pathway. These findings suggest that oridonin may exert anti-cancer effects through the EGFR/PI3K/AKT signalling pathway, providing a robust theoretical foundation for its clinical application and mechanistic investigation in HCC treatment.

Nrf2/NOX2 Pathway Dysregulation and Oxidative Stress Biomarkers in Gaucher Disease–Associated Parkinsonism: Insights Into a Potential Therapeutic Target

Tue, 02 Jun 2026 20:56:18 -0700

ABSTRACT

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, yet its underlying genetic and molecular mechanisms remain incompletely understood. Variants in the GBA gene, encoding the lysosomal enzyme glucocerebrosidase, are not only responsible for Gaucher disease (GD) but also represent a significant genetic risk factor for PD, contributing to lysosomal dysfunction, oxidative stress and autophagy impairment. Among the key regulators of redox homeostasis, the Nrf2/NOX2 signalling axis has emerged as a pivotal pathway in the modulation of neuroinflammation and neurodegeneration. This study aims to explore the pathogenic link between GBA mutations and PD, focusing on the redox imbalance and the role of Nrf2 signalling in an in vivo Gba D409V knock-in (KI) mouse model, compared to wild-type (WT) C57BL/6J controls. Animals 8-weeks old were evaluated over a 3-month period, with tissue and behavioural assessments conducted at 7, 14, 30, 60 and 90 days. Early timepoints (7 and 14 days) did not reveal significant changes in behavioural performance, expression of PD-related markers (TH, DAT, α-synuclein), or oxidative stress indicators, including Nrf2, NOX2, malondialdehyde (MDA) and nitrate/nitrite levels. However, at 30, 60 and especially 90 days, significant alterations emerged, particularly a disrupted Nrf2/NOX2 balance, accompanied by molecular and biochemical signatures of oxidative stress. These findings suggest a time-dependent progression of oxidative alterations in this GD model and support the role of GBA variants in promoting neurodegenerative processes. Unravelling these mechanisms is essential for the identification of early biomarkers and may offer new therapeutic insights for GBA1-associated PD.

GPSM2 Promotes Pancreatic Cancer Progression Through METTL3‐Mediated m6A Modification of YAP1 mRNA

Tue, 02 Jun 2026 20:50:59 -0700

ABSTRACT

Pancreatic cancer poses a major therapeutic challenge due to its insidious onset and difficulty in early diagnosis. G-protein signalling modulator 2 (GPSM2), a member of the G-protein signalling regulator family, is highly expressed in various tumour tissues; however, its role in pancreatic cancer remains largely undefined. Yes-associated protein 1 (YAP1), a transcriptional co-activator, has been recognised as a central node in the growth-promoting signalling pathways of pancreatic cancer. Nevertheless, whether GPSM2 contributes to pancreatic cancer progression through the regulation of YAP1 has not yet been elucidated. In this study, transcriptome analysis of 183 pancreatic cancer patients from The Cancer Genome Atlas (TCGA) dataset identified GPSM2 as a survival-associated gene in pancreatic cancer. Functionally, we demonstrated that GPSM2 promotes colony formation and invasion of pancreatic cancer cells and was found to be mechanistically linked to the regulation of YAP1. Molecular investigations revealed that GPSM2 significantly upregulated YAP1 mRNA levels. Further analysis demonstrated that GPSM2 enhanced the N6-methyladenosine (m6A) modification of YAP1 mRNA in a METTL3-dependent manner. The KH3-4 domain of the m6A reader proteins IGF2BP2 and IGF2BP3 specifically recognised the m6A-modified YAP1 transcripts, thereby stabilising YAP1 mRNA and increasing YAP1 protein expression, which in turn promoted colony formation and invasion in pancreatic cancer cells. These findings provide novel insights into the molecular mechanisms underlying pancreatic cancer progression and may offer promising therapeutic targets for future intervention.

RETRACTION: Spliceosomal Protein E Regulates Neoplastic Cell Growth by Modulating Expression of Cyclin E/CDK2 and G2/M Checkpoint Proteins

Mon, 01 Jun 2026 22:36:57 -0700

RETRACTION: Z. Li and B. M. Pützer, " Spliceosomal Protein E Regulates Neoplastic Cell Growth by Modulating Expression of Cyclin E/CDK2 and G2/M Checkpoint Proteins," Journal of Cellular and Molecular Medicine 12, no. 6a (2008): 2427-2438. https://doi.org/10.1111/j.1582-4934.2008.00244.x.

The above article, published online on 16 December 2008 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stefan Constantinescu; and John Wiley & Sons Ltd. A third party reported that comments had been made on PubPeer [1] that raised concerns about potential duplication of bands in Figure 2B. Additional investigation by the publisher found evidence of splicing in Figure 1B and duplication of Actin blots between Ad-GFP in Figure 3A and Ad-Sme pre-mRNA splicing in Figure 5A. The investigation also found evidence of duplications of the Ad SmE Actin blot in Figure 3A and the Ad-GFP p-CDC2 (Tyr15)/CDC2 blot in Figure 5A. Additional potential duplicated bands were detected in Figure 5A.

The authors responded to an inquiry by the publisher and stated that the Western blots were generated separately for each experiment and were not intentionally duplicated or altered. However, the original data were no longer available due to the time that had elapsed since publication.

The retraction has been agreed to because the evidence of highly similar or duplicated bands fundamentally compromises the editors’ confidence in the results presented. The authors disagree with the retraction.

References

[1] Unregistered Submission and Hydroporus ferrugineus, Comments on “ Spliceosomal protein E regulates neoplastic cell growth by modulating expression of cyclin E/CDK2 and G2/M checkpoint proteins,” PubPeer, May 2016-October 2025. https://pubpeer.com/publications/216D30610A95CE3D109B97FC1CA64D

Commentary on ‘Irisin Attenuates Ventilator‐Induced Diaphragmatic Dysfunction by Inhibiting Endoplasmic Reticulum Stress Through Activation of AMPK’

Wei Li, Hui Yang, Jia Li, Xueqin Xu — Mon, 01 Jun 2026 21:54:37 -0700

Journal of Cellular and Molecular Medicine, Volume 30, Issue 11, June 2026.

Effects of P38 MAPK Pathway Inhibition on the Metabolism of Periodontal Ligament Fibroblasts During Inflammation

Mon, 01 Jun 2026 21:12:41 -0700

ABSTRACT

During the development of periodontitis, osteoclast function is activated by the MAPK pathway. MMPs are able to participate in cross-activation and self-activation cascades, thereby modulating gene expression for osteoclast differentiation. Among the MAPK family, the p38 family has a particularly significant impact on the development of chronic inflammation in periodontal tissue. Activation of p38 MAPK signalling directly or indirectly mediates the expression of inflammatory cytokines, thereby synergistically stimulating MMP production. This experiment aims to understand how p38 MAPK affects inflammatory hPDLFs treated with Pseudomonas gingivalis. Compared with the control group, secretion of MMP-2, −1, and −3 of hPDLFs treated with P. gingivalis-LPS was significantly increased and was closely related to the concentration of P. gingivalis-LPS. Cell scratching and CCK-8 experiments revealed that MMP-1, −2, and −3 inhibited cell proliferation and motility. To explore the signalling pathways involved in p38 MAPK regulation, hPDLFs were treated with P. gingivalis-LPS alone or in combination with a p38 MAPK kinase inhibitor. The results suggest that MMP-1, −2, and −3 can serve as salivary biomarkers for the chronic inflammatory disease periodontitis and regulate inflammation through the p38 MAP kinase pathway.

Integrated Network Pharmacology and Machine Learning to Reveal the Mechanisms of Schisandrin A Against Triple‐Negative Breast Cancer

Mon, 01 Jun 2026 00:34:27 -0700

ABSTRACT

This study aimed to elucidate the mechanism of action of Schisandrin A in the intervention of triple-negative breast cancer (TNBC). Through the application of network pharmacology and the integration of targets from multiple databases, the research identified 128 overlapping targets between Schisandrin A and TNBC. From these, 36 core targets were determined via topological analysis. Utilizing the random forest survival algorithm, four prognosis-related core targets (GSK3B, IDO1, KDR, PKM) were identified from the METABRIC database, and the model's predictive performance was validated using the GSE58812 dataset. Pan-cancer expression analysis confirmed the aberrant expression of these four targets across various tumours. Immune infiltration analysis suggested that GSK3B and IDO1 may influence the tumour immune microenvironment. Molecular docking studies demonstrated a high binding affinity of Schisandrin A with IDO1 and PKM. In vitro cell experiments indicated that Schisandrin A inhibited the proliferation of MDA-MB-231 cells in a concentration-dependent manner, induced apoptosis and caused cell cycle arrest at the S phase. Transcriptome sequencing further revealed the transcriptional changes induced by Schisandrin A, elucidating that the cell cycle and DNA replication are the primary regulatory pathways affected. In conclusion, Schisandrin A exhibits potential anti-triple-negative breast cancer (TNBC) effects by modulating and regulating diverse pathways, including GSK3B and IDO1, alongside its impact on the cell cycle and immune microenvironment. This study presents novel candidate drugs and therapeutic targets for the precise treatment of TNBC.

Tumour Necrosis Factor‐α Promotes Pyroptosis in Diabetic Liver Injury via the HMGB1/TLR4/MyD88/NF‐κB Pathway

Sun, 31 May 2026 00:00:00 -0700

ABSTRACT

Diabetic liver injury (DLI) is a serious inflammatory complication, with tumour necrosis factor-alpha (TNF-α) recognized as a key pro-inflammatory cytokine. This study aimed to investigate the protective effect of TNF-α inhibition on DLI and to elucidate the underlying molecular mechanisms, focusing on the novel role of pyroptosis. An integrated experimental approach was employed, commencing with in vitro studies in HepG2 hepatocytes to dissect the signalling pathway, followed by in vivo validation in Sprague–Dawley rats. In vitro assessments included the expression of pyroptosis-related proteins (caspase1, Gasdermin D [GSDMD]), high mobility group protein B1 (HMGB1), and components of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) pathway under high glucose conditions with or without TNF-α inhibition. In vivo measurements comprised liver function tests alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglycerides (TG), liver histopathology, and analysis of the HMGB1/TLR4/MyD88/NF-κB pyroptosis axis in liver tissues. In vitro, TNF-α inhibition mitigated high glucose-induced hepatocyte pyroptosis and suppressed HMGB1 release and TLR4/MyD88/NF-κB signalling; pharmacological blockade of HMGB1 replicated these effects. In vivo, recombinant human TNF receptor-II:Fc fusion protein (rhTNFR:Fc) significantly improved liver function and histopathology in diabetic rats without affecting blood glucose levels, while also downregulating the expression of HMGB1/TLR4/MyD88/NF-κB pathway components and key pyroptosis markers such as NOD-like receptor family pyrin domain containing 3 (NLRP3). In conclusion, TNF-α promotes DLI by driving hepatocyte pyroptosis through the HMGB1/TLR4/MyD88/NF-κB signalling axis. Inhibition of TNF-α confers potent hepatic protection independent of glycemic control, identifying it as a promising therapeutic strategy for DLI.

Integration of Transcriptomics With Interpretable Artificial Intelligence for Identifying Molecular Signatures of Physiological Stress in Sleep Deprivation

Fri, 29 May 2026 20:53:45 -0700

ABSTRACT

Sleep deprivation induces systemic physiological stress accompanied by transcriptomic remodelling and immune dysregulation, yet objective molecular indicators for its assessment remain insufficient. This study integrated blood transcriptomic analysis with an interpretable machine learning framework to identify and validate candidate molecular signatures associated with sleep deprivation and their potential relevance to insomnia. Publicly available Gene Expression Omnibus datasets were used to construct an acute sleep deprivation training cohort, an independent sleep deprivation validation cohort, and a chronic insomnia validation cohort. Differentially expressed genes were first identified, followed by feature selection using six machine learning algorithms and Shapley additive explanations to improve model interpretability. Immune cell composition was inferred using CIBERSORT, and associations between candidate genes and immune cell subsets were further evaluated. Twenty-five differentially expressed genes were identified in the training cohort, from which eight high-priority candidate genes were selected by the interpretable machine learning framework. Among them, S100A3 showed consistent discriminatory performance across the training cohort, the independent sleep deprivation cohort, and the insomnia cohort, whereas VEGFB exhibited notable diagnostic potential, particularly in insomnia. Immune infiltration analysis indicated that sleep deprivation was associated with altered peripheral immune composition, including reduced resting natural killer cells and activated dendritic cells, together with changes in regulatory and naïve immune cell populations. Expression levels of S100A3 and VEGFB were significantly correlated with specific immune cell subsets, suggesting a link between these molecular signatures and stress-related immunomodulation. These findings identify S100A3 as a robust candidate biomarker shared by acute sleep deprivation and chronic insomnia, while VEGFB may reflect chronic metabolic or inflammatory adaptation. The proposed interpretable transcriptomic-machine learning framework provides a non-invasive strategy for discovering molecular indicators of sleep-related physiological stress and may support future risk stratification in sleep medicine.

Single‐Cell RNA‐Seq Combined With Bulk RNA‐Seq Revealed the Involvement of Pancreatic Cancer Tissue‐Resident Macrophages in Tumour Progression and the Immunotherapy Response

Bin Wu, Chundong Hu, Fengchun Lu — Thu, 28 May 2026 21:10:07 -0700

ABSTRACT

Pancreatic cancer remains a highly lethal malignancy with limited therapeutic efficacy and untapped immunotherapeutic potential, largely constrained by immune cell heterogeneity in the tumour microenvironment. Tumour-associated macrophages (TAMs), especially tissue-resident macrophages (TRMs), exert complex regulatory roles in tumour progression. Here, we integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk-seq) data from the GEO and TCGA databases to characterize macrophage heterogeneity and its functional impacts in pancreatic cancer. We delineated the tumour microenvironment landscape and identified a specific TRM subpopulation. Cell communication analysis revealed extensive interactions between TRMs and other cell types, including CXCL/MIF and notably upregulated SPP1 signalling in tumour tissues. We further established a TAM scoring system and found that clusters 4, 5, 9 and 10 were significantly associated with patient survival. Among them, TRM cluster 4 showed the highest predictive efficacy for 5-year and 10-year mortality, and effectively stratified patients into high- and low-risk groups with distinct differences in survival, immune cell infiltration and immune checkpoint expression. Importantly, TRM_C4 scores exhibited significant changes after immunotherapy, with decreased scores in responders and increased scores in non-responders. Together, our findings demonstrate the critical involvement of pancreatic cancer tissue-resident macrophages in tumour progression and immunotherapy response, and suggest that targeting specific macrophage subpopulations may represent a novel strategy to enhance immunotherapy efficacy and improve clinical outcomes for pancreatic cancer patients.

Myeloid Cell Function and Cytokine Profiles in Paediatric Haemophilia A: Insights From FVIII and Emicizumab Prophylaxis

Wed, 27 May 2026 21:43:27 -0700

ABSTRACT

Haemophilia A (HA) is an X-linked bleeding disorder caused by factor VIII (FVIII) deficiency, treated with FVIII infusions or, more recently, Emicizumab subcutaneously. Although Emicizumab is safe and effective, FVIII is still required for severe bleeding, trauma, or surgery, and few studies have compared these prophylactic options in paediatric patients. This study explores the immunological and haematological profiles of paediatric HA patients receiving FVIII or Emicizumab, using haemophilia B patients and healthy controls. Clinical parameters and immune cell populations showed no major differences aside from age-related variations. However, HA patients displayed higher HLA-DR expression on CD14⁺ cells than healthy controls, and Emicizumab-treated patients showed increased HLA-DR expression on CD11c⁺ cells compared with FVIII-treated patients. Plasma cytokines including IL-12p40, TNF-α, CCL-22, IL-18, and CCL-4 were elevated in HA, suggesting a dysregulated myeloid compartment in HA. Patient-derived macrophages exhibited a stronger pro-inflammatory (M1-like) polarization after in vitro FVIII stimulation, with increased TNF-α and reduced TGF-β gene expression. Stratification by prophylaxis showed that macrophages from FVIII-treated patients maintained the M1 phenotype, whereas those from Emicizumab-treated patients showed no clear shift and tended toward an immune-regulatory profile. These findings highlight distinct myeloid and cytokine signatures associated with different prophylaxis, emphasizing the need for optimized therapeutic strategies.

Issue Information

Mon, 25 May 2026 21:53:49 -0700

Journal of Cellular and Molecular Medicine, Volume 30, Issue 11, June 2026.