Molecular medicine reports最新文献

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by progressive dyspnea. Damage to the lung air‑blood barrier is a major cause of progressive dyspnea observed in COPD. Although cigarette smoke inhalation and repetitive bacterial infection cause and exacerbate COPD, their specific effects on the air‑blood barrier remain to be fully elucidated. The present study explored the effects of the air‑blood barrier in a COPD rat model induced by cigarette smoke inhalation and repetitive bacterial infection. From weeks 1‑8, Sprague‑Dawley rats were treated with cigarette smoke inhalation and repeated Klebsiella pneumoniae exposure. At the end of week 8, lung function, pulmonary pathology, mucin content, inflammation, oxidative stress and MAPK/NF‑κB/IκBα pathway indicators were detected in rats. Lung function parameters, including tidal volume, peak expiratory flow and 50% tidal volume expiratory flow showed significant decreases in COPD model rats. The pulmonary organizational structure and ultrastructure of the air‑blood barrier were also markedly damaged in COPD model rats. Due to cigarette smoke and Klebsiella pneumoniae exposure, the expression of IL‑6, malondialdehyde, mucoprotein (MUC)5AC, MUC5B, matrix metallopeptidase‑9 and angiopoietin‑2 increased in COPD rats, while the expression of IL‑10, tissue inhibitor of metalloproteinases‑1, heme oxygenase‑1, zonula occludens‑1, claudin‑5, aquaporin‑5, surfactant protein‑D and superoxide dismutase significantly decreased. Subsequently, cigarette smoke exposure and Klebsiella pneumoniae infection increased the levels of phosphorylated‑(p‑)p38, p‑ERK, p‑JNK, p‑p65 and p‑IκBα. The present study provided notable evidence that cigarette smoke and Klebsiella pneumoniae exposure exacerbated the destruction of the air‑blood barrier in COPD via the MAPK/NF‑κB/IκBα pathway.

Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible lung condition characterized by airflow limitation. Current treatments primarily aim to alleviate symptoms, especially dyspnea. Extracellular vesicles (EVs), which are nanoscale lipid bilayer particles secreted by living cells, are present in various bodily fluids, including blood, urine and ascites. These vesicles have an important role in intercellular communication and are linked to COPD progression. The present review explores the molecular mechanisms underlying COPD pathogenesis, highlighting the notable involvement of EVs, and also examines the advances that have been made in terms of the diagnostic and therapeutic potential of EVs in COPD management.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the cell morphological images shown in Fig. 3A on p. 988, the second panel on the right (showing the Cela -, TRAIL +, CQ + experiment) was strikingly similar in appearance to a data panel that had been included in a paper published by the same research group 3 years earlier in the journal Oncotarget, although these data were presented in that article in a different scientific context. Moreover, upon assessing the data in this paper independently in the Editorial Office, there were concerns raised about the possible anomalous appearance of the β‑actin blots shown in Fig. 3A, and the Ac‑cas3 blot shown in Fig. 3E. In view of the re‑use of the contentious data in the above paper in a different scientific context, and due to the potentially anomalous appearance of some of the western blot data in this paper, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. 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 19: 984‑993, 2019; DOI: 10.3892/mmr.2018.9757].

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunofluorescence data shown in Fig. 1F, cell viability assay data in Fig. 2F, the 'Control' data for the tissue images relating to apoptotic experiments in Fig. 5B and the 'CHOP/TIPE‑2' histological data in Fig. 5E were strikingly similar to data in articles written by different authors at different research institutes that had either already been published previously in other journals, or which were submitted for publication at around the same time (in the interim, one of those articles has been retracted). In addition, western blot data featured in Fig. 2 were rather similar to data appearing in Fig. 3, suggesting that the same data may have been included in these figures to show the results from purportedly differently performed experiments. The Editorial Office were able to draw the same conclusions as the reader based upon an independent analysis of the contentious data in question. Therefore, owing to the fact that some of these data had already 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 17: 7017‑7026, 2018; DOI: 10.3892/mmr.2018.8789].

Termination of liver regeneration is important for restoring hepatic function after partial hepatectomy (PHx); however, its regulatory mechanisms remain poorly understood. The present study aimed to investigate the role of collagen III (col3) in terminating liver regeneration and its interaction with the β‑catenin signaling pathway. Initially, a 2/3 PHx mouse model was established, and col3 expression dynamics were examined via immunofluorescence and reverse transcription‑quantitative PCR. Collagenase III, also known as matrix metalloproteinase‑13, was used to degrade col3 during the termination phase of liver regeneration, and the resulting effects on hepatocyte proliferation, β‑catenin signaling and liver function were assessed. Methyl‑sulfonyl AB (MSAB), a β‑catenin inhibitor, was used to explore pathway involvement. The present study demonstrated that col3 expression in the parenchymal areas of the liver was decreased during the proliferation phase and increased during the termination phase. Collagenase‑induced col3 degradation enhanced hepatocyte proliferation, delayed regenerative termination, activated β‑catenin signaling, and impaired hepatocyte differentiation and liver function. Administration of MSAB rescued these effects, partially restoring termination and function. In conclusion, col3 may regulate the termination of liver regeneration by suppressing hepatocyte proliferation and promoting functional recovery. These findings provide new insights into collagen‑induced regulation of liver regeneration and potential therapeutic targets for optimizing hepatic recovery.

The present review provided a comprehensive exploration of the subtypes of prolyl hydroxylase domain (PHD) enzymes, with a focus on their localization, regulatory mechanisms and functional roles. Additionally, the development of pharmacological agents targeting PHDs and their crucial involvement in erythropoiesis were examined. Under hypoxic conditions, cells initiate a cascade of adaptive biological responses, numerous of which are governed by the transcriptional complexes of the hypoxia‑inducible factor (HIF) family. The intricate balance among HIF‑1α, HIF‑2α and HIF‑3α plays a fundamental role in orchestrating the transcription of genes involved in red blood cell production, angiogenesis, vascular homeostasis, metabolic regulation, and cellular proliferation and survival. HIF‑1α is rapidly upregulated in response to acute hypoxia and is particularly associated with erythropoietin production, whereas HIF‑2α predominantly regulates adaptive responses to chronic hypoxia. The hydroxylation of HIF‑α at two conserved prolyl residues by PHD1‑3 enables its recognition by the von Hippel‑Lindau tumor suppressor protein E3 ubiquitin ligase complex, leading to its polyubiquitination and subsequent proteasomal degradation. In humans, three PHD isoenzymes (PHD1‑3) and an asparaginyl hydroxylase known as factor‑inhibiting HIF have been identified, each exhibiting distinct substrate specificity and tissue distribution patterns. By modulating the hydroxylation of HIFs, PHDs serve as critical regulators of HIF activity, exerting influence over intracellular metabolism, reactive oxygen species, iron (Fe) bioavailability, nitric oxide signaling and redox equilibrium. These regulatory functions collectively shape a wide range of biological processes under hypoxic conditions. While HIF/PHD inhibitors have been successfully introduced into clinical practice, the development of HIF/PHD activators or functional restorers has faced considerable technical challenges. To date, no studies have reported the discovery of HIF/PHD activators. Nevertheless, targeting the HIF/PHD axis has already shown clinical value in treating anemia associated with chronic kidney disease, and ongoing research may expand its therapeutic potential to other hypoxia‑related disorders. Advancing research in this domain holds promise for pioneering novel therapeutic strategies, particularly for conditions such as polycythemia and chronic mountain sickness, where breakthroughs remain critically needed.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blot data shown in Fig. 2C on p. 5104 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 Oncogene. An independent analysis of the data in this paper made by the Editorial Office further revealed that other western blot data in the same figure had appeared in a number of other papers written by different authors that had also been published previously; furthermore, there were internally duplicated data among the western blots in Figs. 1‑5, and potential anomalies concerning the assembly of the data in these figures. Owing to the fact that the contentious data mentioned above 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: 5100‑5108, 2015; DOI: 10.3892/mmr.2015.4039]

Pancreatic and duodenal homeobox gene 1 (PDX1) is a critical transcription factor involved in pancreatic development and the functionality of mature β‑cells. PDX1 regulates key genes, including insulin and GLUT2, through its DNA‑binding homologous structural domain. In tumors, PDX1 exhibits complex, context‑dependent functions. In pancreatic ductal adenocarcinoma, it transitions from inhibiting follicular cell transformation to promoting tumor proliferation and preventing apoptosis, ultimately inhibiting epithelial‑mesenchymal transition during metastasis. In gastric cancer, PDX1 acts as a tumor suppressor gene, while in esophageal, colorectal, and prostate cancers, it plays a pro‑oncogenic role. Given the dual role of PDX1 in tumorigenesis, its aberrant expression offers potential applications in tumor diagnosis, treatment, and prognosis. The present review explored the structure, function, and mechanisms of PDX1 in tumors, as well as its clinical translational potential, aiming to provide insights for further basic research and pave the way for clinical drug development.

Hepatocellular carcinoma (HCC) often exhibits an immunologically 'cold' tumor microenvironment (TME) characterized by poor T cell infiltration and active immunosuppressive mechanisms, limiting the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs). Therefore, converting immunologically cold HCC tumors into 'hot', immune‑reactive tumors has emerged as a critical strategy to enhance immunotherapy responsiveness. In the present review, the tumor immune landscape in HCC is summarized, and the mechanisms underlying its immunologically cold phenotype, and current strategies for reprogramming the TME toward an immune‑active state are described. In addition, the roles of various immune cells, cytokines and tumor‑intrinsic pathways in driving immune exclusion and tolerance are discussed. Therapeutic approaches include ICI‑based combinations with anti‑angiogenic agents or locoregional therapies, as well as dual checkpoint blockade. Other strategies involve targeting immunosuppressive cell populations, oncolytic virus therapy, cancer vaccines, adoptive cell therapies and epigenetic modulators. Clinical evidence supports the potential of these strategies, with several combinations demonstrating improved response rates and survival. Research aims to optimize these therapies, identify predictive biomarkers and explore novel immune targets to further improve outcomes. Overall, converting HCC from an immunologically cold‑to‑hot tumor represents a promising paradigm to potentiate immunotherapy efficacy, although additional studies and innovative strategies are required to achieve durable benefits for a broader population of patients with HCC.

High‑mobility group nucleosomal‑binding domain 2 (HMGN2) is an abundant conserved protein that acts as a non‑histone nuclear DNA‑binding protein. HMGN2 can be released by activated peripheral blood mononuclear cells, CD8+ T cells and γδ T cells, and can induce tumour cell apoptosis. In the present study, receptors of HMGN2 were detected on tumour cell membranes and the mechanism by which HMGN2 induces tumour cell apoptosis was examined. Flow cytometry was used to determine the degree of HMGN2‑induced apoptosis. To identify notable HMGN2 receptors on tumour cells, the present study used immunoprecipitation and mass spectrometry (IP/MS) to identify protein complexes. Western blotting and immunofluorescence were used to confirm interactions between HMGN2 and oligosaccharyltransferase subunit STT3B (STT3B), and to elucidate the downstream regulatory mechanism of HMGN2. The predictive tools ZDOCK and AlphaFold3 were used to determine the binding conformation of HMGN2 to STT3B. HMGN2 was shown to bind to the membrane and induce the apoptosis of CAL‑27 tumour cells. STT3B was identified via IP/MS as a receptor of HMGN2 on the CAL‑27 membrane and subsequently identified as an important receptor of HMGN2 via an anti‑STT3B blocking assay. ZDOCK and AlphaFold3 analyses revealed that HMGN2 and STT3B formed a stable protein docking model. After incubation with HMGN2, the expression of programmed cell death 1 ligand 1 (PD‑L1)/caspase‑1/gasdermin D (GSDMD) axis components was significantly increased, and PD‑L1 was translocated into the nucleus from the membrane of CAL‑27 cells. The results of the present study indicated that extracellular HMGN2 induced pyroptosis in tumour cells by modulating the STT3B/PD‑L1/caspase‑1/GSDMD axis.