JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

Red blood cells (RBCs) contain the highest purine nucleoside phosphorylase (PNP) level per cell volume, yet the role of PNP in the pathogenesis of sickle cell disease (SCD) is incompletely understood, highlighting an important gap in our knowledge of the disease. Previously, we reported increased PNP release by RBCs and accelerated purine nucleoside metabolism with increased production of pro-oxidant, pro-inflammatory and vasculotoxic byproducts in children with SCD and animal models of hemolytic injury. Thus, we hypothesized that PNP inhibition would reduce hemolysis and attenuate end-organ damage in SCD. In adult patients with SCD (n = 63), plasma PNP levels were markedly elevated compared to controls (n = 27; p < 0.001) and correlated positively with LDH (r = 0.6032, p < 0.0001) and negatively with haemoglobin (r = −0.4523, p = 0.0002). SCD mice also showed accelerated purine metabolism compared to controls. Treatment with the PNP inhibitor 8-aminoguanosine (8-AG) increased inosine and guanosine and reduced downstream vasculotoxic byproducts hypoxanthine (p = 0.036), xanthine (p = 0.004) and guanine (p = 0.047), indicating efficient PNP inhibition. 8-AG treatment rebalanced the purine metabolome in SCD mice to favour protective over harmful purine metabolites without negatively affecting haematological parameters. This was associated with reduced hemolysis and decreased splenomegaly, hepatomegaly, and hepatic and renal injury. This study suggests that PNP is an important erythrocytic damage-associated molecular pattern molecule involved in the complex pathophysiology of SCD and proposes PNP inhibitors as a new therapeutic option for SCD and other hemolytic diseases.

This study evaluated the effect of ascorbic acid (AA) combined with dihydroartemisinin (DHA) in lung adenocarcinoma (LUAD) and the underlying mechanisms to determine whether this combination therapy provides a new therapeutic direction for the treatment of LUAD. The CCK-8, colony formation and transwell assays were used to assess the vitality, proliferation, invasion and migratory capabilities of LUAD cells after various treatments. Furthermore, a xenograft study was performed to assess the effects on tumour inhibition. Transmission electron microscopy (TEM) was used to investigate the changes in mitochondrial architecture in LUAD cells. Additionally, the levels of reactive oxygen species (ROS), divalent iron, malondialdehyde (MDA), mitochondrial membrane potential, and glutathione (GSH) in LUAD cells were quantified using a detection assay kit. GPX4 and SLC7A11 expression levels were assessed using immunohistochemistry, western blotting, and quantitative polymerase chain reaction. The study results showed the inhibitory effect of AA plus DHA on the viability and progression of tumour cells in vitro; the combined therapy reduced cell proliferation, increased cell death, restricted cell invasion and migration, and significantly reduced tumour development in vivo. Furthermore, we observed an excess of iron inside cells, accumulation of ROS, over-expression of MDA, a reduction in the mitochondrial membrane potential, and depletion of GSH in response to combined therapy. Three ferroptosis-related inhibitors partially reversed AA plus DHA-induced cell death. TEM showed changes associated with ferroptosis in the mitochondria. In addition, the administration of AA with DHA reduced the expression of SLC7A11 and GPX4. Finally, the abovementioned effects of ferroptosis could be regulated by influencing the SLC7A11 gene and GPX4. To our knowledge, this is the first study to show that AA and DHA induced ferroptosis in LUAD via the SLC7A11/GPX4 signalling pathway.

Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide. Unlike conventional treatments, the targeted therapies or emerging immunotherapies have shown significant advantages in the management of advanced lung cancer. Therefore, exploring novel predictive biomarkers or therapeutic targets is still of far-reaching significance for the future treatment of lung cancer. This study revealed that low expression of IGSF10, an important member of the immunoglobulin superfamily, significantly correlates with poor overall survival of lung adenocarcinoma (LUAD) patients and strong tumorigenic capacity of LUAD cells. Mechanistically, high expression of IGSF10 can inhibit the epithelial-mesenchymal transition of LUAD cells via p53-triggering ferroptosis and impede G₁/S cell cycle transition of LUAD cells via the p53-p21 axis, leading to suppression of LUAD cell migration, growth and tumorigenic capacity. Our findings clarified the specific role of IGSF10 in LUAD, and theoretically suggested new avenues for the presumable IGSF10-targeting therapy of lung cancer in the future.

Waldenström macroglobulinaemia (WM) is a rare lymphoplasmacytic disease that is hallmarked by B-cell infiltration of the bone marrow, an overexpression of IgM class antibodies and an activating mutation of MYD88 (L265P). The therapeutic options for WM patients include a combination of Rituximab (anti-CD20 monoclonal antibody) and chemotherapy, with newer treatments like proteasomal inhibitors and Bruton's Tyrosine Kinase (BTK) inhibitors showing high levels of success both as monotherapy and in combinations. To date, WM remains incurable. Understanding the basic physiology of WM and creating new and improved pre-clinical models which better reflect the true physiology of WM will allow for the identification of novel therapeutic vulnerabilities and the ability to test these next generation therapies, both in a tumour intrinsic and extrinsic manner. In this review, we aim to provide a comprehensive summary of WM, focusing on the genetic mutations and signalling pathways driving disease progression. In addition, we highlight the current therapeutics and emerging clinical trials to provide novel insights to drive deep and durable responses.

Infection is still one of the biggest threats to global health. Today, treating infections such as osteomyelitis is challenging due to the rise in drug-resistant and biofilm-forming pathogens. Therefore, researchers worldwide are seeking new ways to combat these infections. Nanotechnology, which is of interest in the medical field, has provided a platform for drug delivery and the treatment of osteomyelitis. Various biological, chemical, and physical methods are used for the biosynthesis of nanoparticles. Among these methods, biological methods, or green synthesis, are of great interest due to their non-toxicity, high stability, low cost, and environmental friendliness. This study aimed to investigate nanoparticles biosynthesised from natural sources and use them for the treatment of osteomyelitis.

RETRACTION: A. Mirzaei, R. Mashhadi, Z. Aghsaeifard, M. Izadi, S. N. H. Dougaheh, R. Omid, F. Guitynavard, P. Nikoofar, and S. M. K. Aghamir, “ Sex-Dependent Paracrine Effect of Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells on Prostate Cancer Cells,” Journal of Cellular and Molecular Medicine 29, no. 9 (2025): e70569, https://doi.org/10.1111/jcmm.70569.

The above article, published online on 12 May 2025 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between; the authors; the journal Editor-in-Chief, Stefan N. Constantinescu; the Foundation for Cellular and Molecular Medicine; and John Wiley & Sons Ltd. The retraction has been agreed upon following concerns raised by a third-party regarding image duplication. The investigation confirmed an overlap between the LNCaP MCM and FCM images in Figure 2. In addition, the DU145 and LNCaP control images in Figure 3 were found to be identical. The authors fully cooperated with the investigation, explaining that the duplication was due to an inadvertent error in figure preparation. They also provided some data; however, the data provided was insufficient to restore the editor's confidence in the results and conclusions. Consequently, the editors consider the findings unreliable.

Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, posing a severe threat to female health. Previous research indicates that cuproptosis is a copper-dependent form of regulated cell death, holding potential as a therapeutic avenue. This study aimed to identify and validate Cuproptosis-Related Genes (CRGs) as biomarkers and therapeutic targets in cervical cancer. Transcriptomic data from TCGA and GTEx databases were analysed alongside curated literature data, leading to the identification of 67 pivotal CRGs. Diagnostic and prognostic models were constructed using machine learning algorithms and LASSO-Cox regression, respectively. Glutathione synthetase (GSS) was selected for subsequent functional validation in cellular assays. Drug sensitivity analysis, mechanistic investigations and in vivo experiments were conducted to evaluate therapeutic potential. Statistical analyses were performed using R and GraphPad Prism. Our analysis identified GSS as a core gene. Functional experiments showed that GSS promotes cervical cancer cell proliferation and invasion under cuproptosis-inducing conditions. Drug sensitivity analysis linked GSS to vorinostat, which inhibits tumour growth by suppressing the PI3K/Akt pathway and downregulating GSS. These findings were confirmed in both in vitro and in vivo studies. This study identifies GSS as a key cuproptosis regulator and a promising therapeutic target in cervical cancer, suggesting a novel precision medicine strategy.

In this study, we aimed to get a better understanding of which genes are involved in cartilage damage in KOA and the pathological mechanisms. RNA-seq for cartilage tissues obtained from Normal rats and KOA rats, for IL-1β-stimulated chondrocytes and IL-1β-stimulated chondrocytes treated with TNN recombinant protein, was conducted respectively. The degree of cartilage injury was evaluated by HE and Safranin O-fast green staining, and the expression abundance of TNN and p-AMPK in cartilage tissue or chondrocytes was observed by immunofluorescence. TNN was inhibited in vivo and in vitro by lentivirus and siRNA, respectively. The gene and protein levels of protease MMP3, MMP13, ADAMTS4, and ADAMTS5 and AMPK/PPAR-γ pathway-related factors -AMPK, AMPK, PPAR-γ, PGC-1α, mTOR were detected by PCR and WB, respectively. The mitochondrial membrane potential of chondrocytes was evaluated by JC1 probe, and the oxygen level of chondrocytes was evaluated by ROS immunofluorescence. RNA-seq revealed TNN was significantly up-regulated in the KOA group, and DEGs were mainly enriched in ‘extracellular matrix’. Subsequently, TNN inhibition could reduce the expression of MMPs, ADAMTSs were demonstrated in vivo and in vitro. Further on, RNA-seq on IL-1β-stimulated chondrocytes and chondrocytes treated with TNN recombinant protein after IL-1β stimulation confirmed that AMPK-PPARγ signalling might be the downstream pathway of TNN, and the negative regulation of TNN on AMPK-PPARγ signalling was observed in vivo and in vitro. This study innovatively unveils the increased TNN in KOA accelerates cartilage damage, and this damage-promoting effect is achieved by negative regulation of AMPK-PPARγ signalling.

Asthma is a chronic inflammatory respiratory disorder triggered by allergens or environmental pollutants, characterised by airway obstruction, increased airway resistance and breathing difficulties. Although substantial progress has been made in elucidating its pathophysiology, the molecular mechanisms underlying asthma progression remain incompletely understood, and no curative therapies are currently available. The present study explored the role of KIF1B (kinesin family member 1B) in asthma pathogenesis using integrated approaches involving human cohort datasets, in vitro airway epithelial cell models and an in vivo ovalbumin (OVA)-induced asthma mouse model. KIF1B knockdown and NLRP3 (NLR family pyrin domain-containing 3) overexpression assays were performed to delineate the molecular mechanisms by which KIF1B modulates pyroptosis. Results showed that KIF1B expression was markedly elevated in bronchial biopsies from asthma patients, OVA-challenged mouse lungs and IL-13–stimulated BEAS-2B cells. Silencing KIF1B significantly attenuated OVA- and IL-13–induced oxidative stress, proinflammatory cytokine release and pulmonary injury. Specifically, KIF1B knockdown reduced the expression of pyroptosis-associated proteins—NLRP3, cleaved caspase-1 and cleaved gasdermin D (GSDMD)—while decreasing TNF-α, IL-1β and IL-18 levels and restoring the anti-inflammatory cytokine IL-10. Mechanistically, NLRP3 overexpression abolished the anti-inflammatory and cytoprotective effects of KIF1B silencing, confirming that KIF1B promotes asthmatic inflammation through activation of the NLRP3 inflammasome. In conclusion, these findings identify KIF1B as a key regulator of airway inflammation and pyroptosis in asthma via NLRP3-dependent signalling. Targeting KIF1B may therefore represent a promising therapeutic strategy for controlling asthma progression.

Myocardial infarction (MI) is a sudden necrosis of cardiomyocytes, often caused by atherosclerosis, with obesity being a significant risk factor. This study aimed to evaluate the effects of a high-fat diet (HFD) on post-MI myocardial remodelling, focusing on inflammatory signalling, nitric oxide synthase (NOS) dysregulation and oxidative stress. Nine-week-old Wistar Kyoto rats fed a control diet or a HFD for 4 weeks, followed by 20 min of left descending coronary artery occlusion and 7 days of reperfusion. Plasma levels of the proinflammatory cytokines TNF-α and IL-6 were measured using a Bioplex kit. NOS activity was assessed via [³H]-l-citrulline production, while the expression of eNOS, iNOS, NFκB and TLR4 in cardiac tissue was analysed by Western blot. Lipid peroxidation was assessed by measuring conjugated diene concentrations in cardiac tissue. MI and HFD both increased proinflammatory cytokine levels, reduced NOS activity and eNOS expression and increased iNOS expression. NFκB was more highly expressed after MI in control-fed animals. Notably, TLR4 expression was reduced by HFD and remained unchanged post-MI. Conjugated dienes were elevated post-MI and further increased by HFD. These findings demonstrate that HFD exacerbates post-MI inflammation and oxidative stress, impairing nitric oxide signalling and promoting adverse cardiac remodelling.