Molecular medicine reports最新文献

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the statistical analysis in this study may not have employed the most appropriate statistical tests; namely, the paired Student's t‑test was used for comparisons between independent groups, which the reader considered may have inflated the statistical significance. Neither may the paired Student's t‑test have been the most appropriate test to have been selected for various of the migration and invasion assay experiments, wherein at least three groups were being compared. Owing to the fact that the Editorial Office has been made aware of the possibility of inappropriate statistics handling in this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Molecular Medicine Reports 1: 641‑646, 2008; DOI: 10.3892/mmr_00000005].

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, in addition to the duplication of a pair of data panels in Fig. 7A, flow cytometric (FCM) assay data featured in Figs. 2D and 6B were strikingly similar to FCM data which were ultimately published in a number of other papers in different journals that were written by different authors at different research institutes, including a paper that was submitted on an earlier date to the journal Experimental and Therapeutic Medicine. Owing to the fact that the contentious data in the above article were found to be strikingly similar to data that have appeared elsewhere in other papers in the scientific literature, 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 20: 3149‑3159, 2019; DOI: 10.3892/mmr.2019.10563].

Urethral injury is a common type of traumatic damage to the urinary system, often leading to urethral stricture, fibrosis and dysfunction, which significantly impair physiological function and quality of life. The present study aimed to investigate the therapeutic efficacy of the novel immune‑regulatory molecule tetrahedral DNA nanostructure (TDN) in a rat model of urethral injury and explore the underlying mechanisms of action. A rat model of urethral injury was established through mechanical injury. Animals were divided into four groups: Control, model, model + rapamycin and model + TDN. Therapeutic effects and associated mechanisms were assessed via retrograde urethrography, Masson's trichrome staining, immunohistochemistry, western blotting, reverse transcription‑quantitative PCR (RT‑qPCR) and transcriptomic analysis. The results revealed that TDN markedly alleviated the immune response after urethral injury, reduced immune cell infiltration, downregulated the expression of inflammatory cytokines, including IL‑6, IL‑1β and TNF‑α, and effectively inhibited the progression of fibrosis. Masson's trichrome staining and western blotting provided evidence of reduced collagen deposition and decreased expression of fibrosis markers, including α‑smooth muscle actin, TGF‑β1, collagen I, collagen III and Smad3, after treatment with TDN. Transcriptomic analysis revealed that TDN modulated multiple immune‑related pathways, including the NF‑κB signaling pathway, NOD‑like receptor signaling pathway and cytokine‑cytokine receptor interaction, accompanied by a decrease in immune‑inflammatory responses, such as reduced inflammatory cytokine production and immune cell infiltration. Additionally, the results suggested that TDN may improve cellular metabolism and inhibit cell proliferation by downregulating the expression of cell cycle‑associated genes, as demonstrated by transcriptomic analysis and RT‑qPCR validation of cyclin B1, ribonucleotide reductase regulatory subunit M2, polo‑like kinase 1 and cyclin‑dependent kinase 1. In conclusion, TDN notably promoted tissue repair after urethral injury in rats by regulating the immune response, inhibiting fibrosis and enhancing cellular metabolism. These findings highlight TDN as a promising therapeutic candidate for urethral injury and offer novel insights into immune-regulatory strategies for the treatment of other fibrotic diseases.

Cardiac hypertrophy is associated with ferroptosis. Serine/threonine protein kinase ULK1 (ULK1) acts as a key activator of autophagy; however, its exact function in the non‑autophagy pathway remains to be fully elucidated. The present study aimed to decipher the role and mechanisms of ULK1 in ferroptosis and cardiomyocyte hypertrophy. Cell survival, lipid peroxidation, iron metabolism and prostaglandin endoperoxide synthase 2 (Ptgs2) mRNA expression were analyzed to investigate the role of ferroptosis in ULK1‑silenced or ULK1‑overexpressing HL‑1 cells. Immunofluorescence staining, western blot analysis and monomeric red fluorescent protein‑green fluorescent protein‑microtubule‑associated protein 1 light chain 3 puncta formation assays were performed to demonstrate the regulatory effect of ULK1 on autophagy and ferritinophagy‑related proteins. Ferritinophagy activation was assessed in cardiomyocytes using immunofluorescence of nuclear receptor coactivator 4 (NCOA4) and microtubule‑associated protein 1 light chain 3‑II colocalization. ULK1 expression was found to be elevated in both transverse aortic constriction‑induced hypertrophic cardiac tissues and angiotensin II‑treated cardiomyocytes. ULK1 knockdown markedly suppressed cardiomyocyte ferroptosis, whereas ULK1 overexpression facilitated ferroptosis in HL‑1 cells. Meanwhile, the ferroptosis inhibitor ferrostatin‑1 reduced iron accumulation, lipid peroxidation and Ptgs2 mRNA expression. Notably, the autophagy inhibitor 3‑methyladenine mitigated ULK1‑induced ferroptosis. Mechanistically, ULK1‑activated NCOA4‑mediated ferritinophagy was found to be dependent on the Beclin1/PI3K catalytic subunit type 3 complex. Finally, the ULK1 inhibitor SBI‑0206965 ameliorated ferroptosis in cardiomyocytes in vitro. For the first time, to the best of our knowledge, the present study demonstrated that ULK1 modulates NCOA4‑mediated ferritinophagy and ferroptosis in HL‑1 cells. The findings of the present study provide a novel insight into the progression of cardiomyocyte hypertrophy.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric data shown in Fig. 5A on p. 4978 were strikingly similar to data that had either appeared previously in other papers written by different authors at different research institutes, or which had already been submitted for publication. 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 20: 4973‑4983, 2019; DOI: 10.3892/mmr.2019.10737].

Intervertebral disc degeneration (IDD) is a major pathological basis for spinal degenerative diseases, involving mechanisms such as abnormal mechanical loading, inflammatory responses, and genetic and environmental factors. The role of epigenetic regulation in IDD has gained attention as a potential therapeutic target. The present review systematically explores the contributions of DNA methylation, histone modifications, non‑coding RNAs (ncRNAs) and metabolic regulation to IDD progression, and elucidates their molecular mechanisms. Specific examples include: DNA methyltransferase 3β‑mediated DNA methylation promoting ferroptosis and oxidative stress in nucleus pulposus cells; enhancer of zeste homolog 2 (EZH2)‑mediated trimethylation of histone H3 lysine 27 modification inhibiting SOX9 expression, leading to cellular senescence and extracellular matrix degradation; and ncRNAs (such as microRNA‑143 and LINC01121) regulating gene transcription to affect inflammation and apoptosis. Additionally, metabolic products (such as NAD+, α‑ketoglutarate and lactate) interact with epigenetic pathways to influence IDD. Specifically, NAD+ acts as a cofactor for sirtuin deacetylases, thereby regulating histone and non‑histone protein acetylation; α‑ketoglutarate serves as a cofactor for TET DNA demethylases and Jumonji‑C histone demethylases, influencing DNA and histone demethylation; and lactate induces histone lactylation, which modulates gene transcription related to inflammation and extracellular matrix metabolism in IDD. Based on these mechanisms, novel therapies targeting epigenetics (such as DNA methylation inhibitors, EZH2 inhibitors and RNA interference) show therapeutic potential. Future research should further explore the crosstalk between epigenetic and metabolic regulation to advance the development of personalized and precision medicine strategies for IDD intervention.

Infantile hemangioma (IH) is a type of benign vascular tumor observed in younger patients. Previously, 216 differentially expressed microRNAs (miRs/miRNAs) associated with IH have been identified. In addition, common hub genes and miRNAs related to proteoglycan signaling pathways in angiogenesis and cancer have been identified, including c‑Myc, integrin β1 (ITGB1), Bcl2 and miR‑29a. Therefore, the present study aimed to explore the pathogenesis of IH from the perspective of previously identified miRNA gene network and protein‑protein interactions. Gene and protein levels in human umbilical vein endothelial cells (HUVECs) were analyzed using reverse transcription‑quantitative PCR and western blot (WB) analysis. Cell viability was assessed using a Cell Counting Kit‑8 assay, and the potential association between miR‑29a with ITGB1 was validated using a dual‑luciferase reporter assay. The inhibition of ITGB1 suppressed the β‑catenin/c‑Myc pathway in HUVECs. In addition, transfection with small interfering RNAs (siRNAs) targeting ITGB1 decreased the viability of HUVECs. Furthermore, siRNAs targeting mucin 1 and β‑N‑acetylglucosaminidase significantly inhibited the c‑Myc pathway in HUVECs. The results of WB and dual‑luciferase reporter assays demonstrated that miR‑29a regulated the β‑catenin/c‑Myc pathway and the viability of HUVECs in HUVECs by directly binding to ITGB1. Therefore, miR‑29a may serve as a potential therapeutic target for IH.

Tubulointerstitial injury is a key driver of lupus nephritis (LN) progression, and dysregulation of the immune microenvironment is a central feature of this process. The molecular mediators of this dysregulation remain incompletely defined. In the present study an integrated bioinformatics and experimental analysis was performed of the Activator Protein 1 (AP‑1) family transcription factor Fos‑related antigen 1 (FRA1) in LN tubulointerstitium. Analysis of gene expression omnibus datasets (GSE113342, GSE200306 and GSE127797) showed that FRA1 was markedly upregulated in the tubulointerstitium of LN samples and that its expression positively correlated with CD8⁺ T cells, regulatory T cells, monocytes, M1 macrophages and activated mast cells, but negatively correlated with plasma cells, resting CD4⁺ memory T cells, M0/M2 macrophages, resting dendritic cells and resting mast cells. In vivo experiments revealed that, FRA1 expression was also increased in kidneys from MRL/lpr mice. Furthermore, in vitro, lentiviral overexpression of FRA1 in HK‑2 cells induced robust upregulation of IL‑6, IL‑1β, IL‑8, MCP‑1 and RANTES, whereas FRA1 knockdown selectively decreased IL‑6 and RANTES levels. Together, these results indicate that FRA1 is significantly elevated in the LN tubulointerstitium and may foster a proinflammatory microenvironment by regulating key cytokines. The FRA1/AP‑1 axis therefore represents a potential regulator of renal inflammation in LN and a candidate therapeutic target.

Neuroinflammation is a central component of the pathophysiology of ischemic stroke (IS). Suppressing excessive inflammatory responses after stroke can markedly improve patient outcomes. Interleukin‑6 (IL‑6), a key mediator of the inflammatory cascade, serves a notable role in the pathological process of acute IS through multiple mechanisms. Elevated serum IL‑6 levels serve as an important biomarker for predicting the onset and recurrence of IS and are closely associated with disease severity and prognosis. Anti‑inflammatory interventions are notably important during the acute phase and secondary prevention of stroke. Currently, therapeutic strategies targeting the IL‑6/IL‑6R signaling axis are under investigation and have shown promising clinical potential. The present review summarizes the important role of IL‑6 in neuroinflammation associated with IS, its association with disease severity and prognosis and previous advances in anti‑inflammatory therapeutic strategies targeting the IL‑6/IL‑6R pathway during both the acute phase and secondary prevention of IS.

Following the publication of the above paper, the authors contacted the Editor to explain that they had made a couple of inadvertent errors in assembling the data in Figs. 1B and 2B. Specifically, the following issues were identified: first, the immunohistochemical staining images representing CD31 in Fig. 1B on p. 3434 were chosen from the wrong dataset; secondly, the immunohistochemical staining images representing HIF‑1α in Fig. 2B on p. 3435 were similarly included in this figure incorrectly. After having performed an  independent analysis of these data in the Editorial Office, it came to light that certain of the data featured in Fig. 2B had been submitted for publication at around the same time in an article featuring some of the same authors to the journal PLoS One. However, the authors were able to consult their original data, and the revised versions of Figs. 1 and 2, now featuring all the correct data for Figs. 1B and 2B, are shown on the next two pages. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 12: 3432‑3438, 2015; DOI: 10.3892/mmr.2015.3815]