Molecular medicine reports最新文献

The DNA topoisomerase isoform topoisomerase IIα (TOP2A) is essential for the condensation and segregation of cellular mitotic chromosomes and the structural maintenance. It has been demonstrated that TOP2A is highly expressed in various malignancies, including lung adenocarcinoma (LUAD), hepatocellular carcinoma (HCC) and breast cancer (BC), associating with poor prognosis and aggressive tumor behavior. Additionally, TOP2A has emerged as a promising target for cancer therapy, with widespread clinical application of associated chemotherapeutic agents. The present study explored the impact of TOP2A on malignant tumor growth and the advancements in research on its targeted drugs. The fundamental mechanisms of TOP2A have been detailed, its specific roles in tumor cells are analyzed, and its potential as a biomarker for tumor prognosis and therapeutic targeting is highlighted. Additionally, the present review compiles findings from the latest clinical trials of relevant targeted agents, information on newly developed inhibitors, and discusses future research directions and clinical application strategies in cancer therapy, aiming to propose novel ideas and methods.

Metabolic reprogramming is a prominent characteristic of tumor cells, evidenced by heightened secretion of lactate, which is linked to tumor progression. Furthermore, the accumulation of lactate in the tumor microenvironment (TME) influences immune cell activity, including the activity of macrophages, dendritic cells and T cells, fostering an immunosuppressive milieu. Anti‑programmed cell death protein 1 (PD‑1)/programmed death‑ligand 1 (PD‑L1) therapy is associated with a prolonged survival time of patients with non‑small cell lung cancer. However, some patients still develop resistance to anti‑PD‑1/PD‑L1 therapy. Lactate is associated with resistance to anti‑PD‑1/PD‑L1 therapy. The present review summarizes what is known about lactate metabolism in tumor cells and how it affects immune cell function. In addition, the present review emphasizes the relationship between lactate secretion and immunotherapy resistance. The present review also explores the potential for targeting lactate within the TME to enhance the efficacy of immunotherapy.

In patients with idiopathic pulmonary fibrosis (IPF), the role of 5‑methylcytosine (m5C)‑associated genes in the pathogenesis and development of the disease remains unclear. The present study aimed to identify reliable diagnostic markers based on the expression of m5C‑associated genes for the early detection of IPF. Count data were obtained by screening the IPF genome‑wide assay in the Gene Expression Omnibus database, followed by a comparison of m5C gene expression in patients with IPF and controls. The GSE150910 and GSE173355 datasets yielded a total of 23 differentially expressed m5C‑associated genes, which were then investigated for their functions. A diagnostic model was built using eight m5C genes and validated with training sets and the GSE124685 dataset. IPF subtypes were identified based on expression of m5C‑related genes as well as clinical and immunological characteristics. Furthermore, a pulmonary fibrosis model was established in mice by administering bleomycin into the trachea. Lungs were harvested and analyzed using quantitative PCR to determine the expression of m5C‑related genes. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these genes were significantly enriched in 'base excision repair'. Immunoassay results revealed that 13 immune cell markers (naive, memory and B cell plasma, T cell CD4 naive, T cell CD4 memory resting, T cell follicular helper, T cell regulatory Tregs, NK cell resting, Monocyte, Macrophage M0, Mast cell activated, Eosinophil, and Neutrophil) were significantly associated with IPF. Patients with IPF had lower levels of resting memory CD4+ T cells, which were positively associated with Tet methylcytosine dioxygenase2 (TET2) and Thymine‑DNA glycosylase (TDG) but negatively correlated with NOP2/Sun RNA methyltransferase5 (NSUN5) expression. All samples were classified into based on the levels of the eight diagnostic m5C genes. Samples with high m5C scores are subtype 1, and those with low m5C scores are subtype 2. In subtype 2, male patients had lower levels of CD27 and CD70 but higher levels of CD274, CD86, Cytotoxic T‑lymphocyte‑associated protein4 and Hepatitis A virus cellular receptor2 (HAVCR2). When compared with normal mouse lung tissue samples, expression levels of NOP2/Sun RNA methyltransferase6 (NSUN6), Ubiquitin‑like with PHD and RING Finger Domains1, TDG and TET2 in lung fibrosis tissue samples were significantly higher, while expression levels of NSUN5, NTH‑like DNA glycosylase1, DNA (cytosine‑5‑)‑methyltransferase3 β and Methyl‑CpG binding domain protein 3) were lower. It is possible that m5C‑associated genes play an important role in the diagnosis and typing of IPF. These genes may facilitate investigation of the pathophysiology of IPF and identification of potential treatment targets.

Adjacent segment disease (ASD) is a significant clinical complication following cervical and lumbar spinal fusion surgery, characterized by the degeneration of spinal segments adjacent to the fused area. The present literature review aimed to elucidate the risk factors contributing to ASD and to evaluate current and emerging treatment strategies. Epidemiological data indicate that patient‑related factors such as age, pre‑existing spinal degeneration and comorbidities, along with surgical factors including the type of fusion, instrumentation and alignment correction, play pivotal roles in ASD development. Biomechanical alterations post‑fusion further exacerbate the risk. The underlying mechanisms of ASD involve changes in spinal kinematics and disc degeneration, driven by inflammatory and degenerative processes. Diagnostic modalities, such as magnetic resonance imaging and computed tomography scans, are essential for early detection and accurate diagnosis. Preventive strategies emphasize meticulous preoperative planning, advanced surgical techniques and postoperative rehabilitation. Treatment approaches range from conservative methods such as physical therapy and pharmacological interventions to surgical solutions, including revision surgeries and the use of motion‑preserving technologies. Emerging therapies, particularly in regenerative medicine, show promise in mitigating ASD. The present review underscored the necessity of a multidisciplinary approach to optimize patient outcomes and highlighted the need for ongoing research to address gaps in the current understanding of ASD in both cervical and lumbar regions.

The present study investigated the therapeutic potential of Stattic, a selective inhibitor of STAT3, in treating T‑cell acute lymphoblastic leukemia (T‑ALL). The effects of Stattic on cell viability, STAT3 phosphorylation, apoptosis and autophagy in T‑ALL cell lines, and on tumor growth in a xenograft mouse model of T‑ALL, were assessed. Methods, including the Cell Counting Kit‑8 assay for cell viability, propidium iodide/Annexin V staining for apoptosis detection, western blotting for protein expression analysis, and a xenograft mouse model for evaluating in vivo tumor growth, were employed. The results showed that Stattic effectively reduced cell viability in a dose‑dependent manner, with significant reductions observed at concentrations of 1.25 µM and above in CCRF‑CEM cells (IC₅₀=3.188 µM) and at 2.5 µM and above in Jurkat cells (IC₅₀=4.89 µM) after 24 h of treatment. Concurrently, Stattic significantly suppressed the expression of phosphorylated STAT3, indicating its mechanism of action as a STAT3 pathway inhibitor. Furthermore, Stattic treatment induced both apoptosis and autophagy in CCRF‑CEM and Jurkat cells, as evidenced by the respective upregulation of cleaved caspase‑3 and LC3B. In a xenograft mouse model of T‑ALL, Stattic markedly inhibited tumor growth, with the greatest effect occurring at the highest dose of 30 mg/kg. These results suggested that Stattic holds promise as a therapeutic agent in T‑ALL by modulating key pathways involved in cell survival and proliferation. In conclusion, Stattic exhibited a significant therapeutic potential for T‑ALL via a dose‑dependent reduction of cell viability, inhibiting STAT3 phosphorylation, and promoting both apoptotic and autophagic cell death; however, further studies are required before clinical application.

The occurrence of epilepsy is a spontaneous and recurring process due to abnormal neuronal firing in the brain. Epilepsy is understood to be caused by an imbalance between excitatory and inhibitory neurotransmitters in the neural network. The close association between astrocytes and synapses can regulate the excitability of neurons through the clearance of neurotransmitters. Therefore, the abnormal function of astrocytes can lead to the onset and development of epilepsy. The onset of epilepsy can produce a large number of inflammatory mediators, which can aggravate epileptic seizures, leading to a vicious cycle. Neurons and glial cells interact to promote the onset and maintenance of epilepsy, but the specific underlying molecular mechanisms need to be further studied. Ciliary neurotrophic factor (CNTF) belongs to the IL‑6 cytokine family and is mainly secreted by astrocytes and Schwann cells. In the normal physiological state, CNTF levels are low, but in an epileptic state, CNTF levels in the serum and tears of patients are elevated. Astrocyte activation plays an important role in epileptic seizures. CNTF activates astrocytes to produce a variety of secreted proteins, which are secreted into the astrocyte culture medium (ACM), thus forming a distinct culture medium (CNTF‑ACM) that can be used to study the effect of astrocytes on neurons in vitro. CNTF‑activated astrocytes increase the secretion of the pro‑inflammatory factor IL‑6. In the present study, CNTF‑ACM was applied to primary cerebral cortical neurons to observe the specific effects of IL‑6 in CNTF‑ACM on neuronal activity and excitability. The results suggested that CNTF‑ACM can reduce neuronal activity via the IL‑6/IL‑6R pathway, promote neuronal apoptosis, increase Ca²⁺ inflow, activate the large conductance calcium‑activated potassium channel and enhance neuronal excitability. The results of the present study further revealed the functional changes of astrocytes after CNTF activated astrocytes and the effects on neuronal activity and excitability, thereby providing new experimental evidence for the role of communication between astrocytes and neurons in the mechanism of epileptic seizures.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell apoptotic assay data shown in Fig. 2A on p. 4082 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes that had already been published in the journal Life Sciences prior to the submission of this paper to Molecular Medicine Reports. In view of the fact that the abovementioned data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 12: 4079‑4088, 2015; DOI: 10.3892/mmr.2015.3991].

Doxorubicin (DOX) is a principal chemotherapeutic agent in the domain of oncological intervention. However, its clinical application is constrained due to its severe and irreversible side effects, particularly heart damage. Ferroptosis, characterized by iron accumulation and redox system imbalance, serves a key role in DOX‑induced cardiotoxicity. Ophiopogon japonicus polysaccharide (OJP) exhibits diverse pharmacological activities, including cardiovascular protection, and anti‑inflammatory, anti‑oxidative and immune regulatory effects. However, the role and mechanism of OJP in DOX‑mediated ferroptosis‑triggered injury in cardiomyocytes remain elusive. The present study aimed to assess the effect of OJP on DOX‑induced myocardial ferroptosis injury and to reveal its underlying anti‑ferroptosis mechanism. The detection of myocardial injury markers, such as LDH, indicated that OJP can ameliorate myocardial damage. Additionally, western blot analyses reveal that OJP decreases the expression levels of the ferroptosis‑related marker transferrin receptor 1 (TFR1) while simultaneously increasing expression levels of glutathione peroxidase 4 (GPX4) in a concentration‑dependent manner. Furthermore, fluorescence probe assays demonstrate that OJP not only reduces iron accumulation and oxidative stress but also inhibits the production of lipid peroxidation, as evidenced by a decrease in malondialdehyde (MDA) levels measured. In addition, OJP simultaneously decreased ferroptosis by enhancing mitochondrial function. Mechanistically, OJP attenuated ferroptosis by upregulating the endogenous key antioxidant factor nuclear factor erythroid 2‑related factor 2 (Nrf2), which in turn increased the expression of the downstream signaling molecule GPX4 and reduced the accumulation of the labile iron pool. Therefore, OJP may be a novel therapeutic intervention for DOX‑induced ferroptosis‑triggered myocardial injury.

Following the publication of this paper, and subsequently to the publication of a corrigendum (DOI: 10.3892/mmr.2022.12912) that was intended to address the issue of a pair of incorrectly written primer sequences, it was drawn to the Editors' attention by a concerned reader that certain of the cell invasion assay data shown in Fig. 4A on p. 7 were strikingly similar to data appearing in different form in an article written by different authors at different research institutes that had already been published in the journal Journal of Cancer. In view of the fact that the abovementioned data had already apparently been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 23: 318, 2021; DOI: 10.3892/mmr.2021.11957].

The present study investigated the impact of boric acid (BA) and borax (BX) on markers of inflammation and modifications in miR‑21/PTEN/AKT pathway genes in the liver and kidney tissues of Sprague Dawley male rats with sepsis induced by cecal ligation and puncture (CLP). A total of 60 male Sprague Dawley rats were randomly divided into 6 groups, each containing 10 animals as follows: Control, CLP (where the model was created), 20 mg/kg BX (CLP + BX1), 40 mg/kg BX (CLP + BX2), 20 mg/kg BA (CLP + BA1) and 40 mg/kg BA (CLP + BA2). Liver and kidney tissues were analyzed for histopathological changes, immunopositivity for tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑10, and gene expression of microRNA‑21 (miR‑21), phosphatase and tensin homolog (PTEN) and AKT. Gene expression analysis in the liver tissues revealed a significant decrease in miR‑21, and a marked but not significant decrease in PTEN levels in the CLP group, while AKT expression was significantly increased in the CLP group, and was significantly decreased in CLP + BA1 group compared with in the CLP group. In the kidney tissues, miR‑21 levels were significantly decreased in the CLP group, but the CLP + BA2 group showed a significant increase compared with in the CLP group. These results suggest the potential therapeutic benefits of low‑dose BA and BX in ameliorating sepsis‑induced tissue damage, emphasizing the need for further exploration of their mechanisms of action.