JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

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.

Subtalar arthrodesis (SA) is a widely used salvage procedure for posttraumatic subtalar arthritis (PSA), but its underlying healing mechanisms remain poorly understood. The immune system plays a critical role in the union process after arthrodesis; however, the systemic osteoimmunological response has not been clearly defined. In this study, we investigated immune cell dynamics in patients who underwent SA using single-cell RNA sequencing (scRNA-seq). Peripheral blood mononuclear cells (PBMCs) were collected before surgery and 3 months after the operation. The degree of bone fusion was assessed using computed tomography (CT) scans at 3 months, and patients were categorised into early union (EU) and delayed union (DU) groups. scRNA-seq analysis was performed to examine immune cell composition, gene expression and functional pathways. Monocytes in the EU group showed enhanced antigen processing and presentation, whereas those in the DU group demonstrated increased phagocytic activity. NK cells in the DU group exhibited stronger cytotoxicity through Fc-gamma receptor signalling and antibody-dependent cellular cytotoxicity (ADCC) pathways, while NK cells in the EU group showed higher chemokine and cytokine activity. These immune differences persisted postoperatively, suggesting that variations in the systemic immune environment may influence bone healing outcomes. Our findings emphasise the important roles of monocytes and NK cells in bone union and suggest that immunomodulatory approaches could help improve bone repair.

Myocardial ischaemia continues to be a predominant global cause of mortality, leaving survivors with compromised quality of life and significant loss of functional cardiomyocytes. The main therapeutic approach, which attempts to restore heart function, generally involves myocardial reperfusion. However, this intervention is frequently complicated by the occurrence of myocardial reperfusion injury, which undermines its therapeutic benefits. Consequently, there is an increasing focus on alternative regenerative approaches, such as stem and progenitor cell therapies. Since their initial and successful use in oncology, stem cells have emerged as promising tools for mitigating various pathological conditions. Nonetheless, their efficacy in post-ischaemic myocardial environments is questioned due to their rapid degradation following delivery. Interestingly, small extracellular vesicles, particularly exosomes secreted by stem cells, demonstrate reparative properties akin to those of the stem cells themselves. Indeed, evidence strongly shows that exosomes derived from mesenchymal stem cells, cardiac progenitor cells, and induced pluripotent stem cells exert anti-apoptotic and pro-angiogenic effects in post-ischaemic cardiomyocytes while concomitantly offering protection against myocardial reperfusion injury. In this review, we critically appraise the pivotal findings supporting the potential clinical application of stem cell-derived exosomes, and underscore key considerations necessary to optimise their therapeutic efficacy.

Telomeres are repetitive DNA sequences located at the ends of eukaryotic chromosomes, forming protective caps that prevent chromosomal degradation and inappropriate repair during cell division. Telomere shortening has been linked to ageing and various age-related diseases. In this study, we validated the reference range for telomere length established through the analysis of 1011 Korean individuals to confirm its robustness. Telomere length showed a declining trend with increasing age, with no statistically significant differences observed between sexes. Diabetic and dyslipidaemic groups had shorter telomeres than the control group. These findings suggest that telomere length may be a biomarker of biological ageing and could be linked to metabolic conditions. Future research could build upon these observations to explore telomere dynamics in broader populations and investigate their clinical relevance across diverse health outcomes. Furthermore, longitudinal studies are needed to determine whether telomere shortening is a cause or consequence of these metabolic conditions. Additionally, incorporating advanced methodologies, such as next-generation sequencing, could enhance our understanding of telomere biology and improve the accuracy of telomere-based measurements in both research and clinical settings.