Molecular medicine reports最新文献

M1 macrophages activated by cigarette smoke extract (CSE) serve a pro‑inflammatory role in chronic obstructive pulmonary disease (COPD). The expression of silent information regulator 1 (SIRT1) is decreased in the alveolar macrophages of patients with COPD. However, whether SIRT1 is involved in COPD by regulating macrophage polarization remains unknown. Rat Alveolar Macrophage NR8383 cells were exposed to CSE. Cell Counting Kit‑8 assay, western blot assay and ELISA showed that with increasing concentration of CSE, the activity of NR8383 cells and expression of SIRT1 gradually decreased, while the release of inflammatory cytokines TNFα, IL‑1β and IL‑6 increased. As shown in western blot or Immunofluorescence assays, exposure to CSE also increased expression levels of the M1 markers inducible nitric oxide synthase and CD86, whereas it downregulated expression of the M2 markers arginase 1 and CD206. In addition, CSE increased expression of TNF receptor associated factor 6 (TRAF6), NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved caspase‑1 protein in NR8383 cells. Overexpression plasmids of SIRT1 and TRAF6 significantly reversed the aforementioned changes induced by CSE. Moreover, immunoprecipitation demonstrated that TRAF6 could bind to NLRP3. The overexpression of TRAF6 notably attenuated the regulatory effects of overexpression of SIRT1 on polarization and inflammation in NR8383 cells. Conversely, overexpression of SIRT1 inhibited the TRAF6/NLRP3 signaling pathway, thereby suppressing CSE‑induced M1 polarization and release of inflammatory factors in NR8383 cells. The present study demonstrates that SIRT1 regulates CSE‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway.

Tissue factor (TF) possesses additional physiological functions beyond initiating the coagulation cascade. Cellular signals initiated by cellular TF or on contact with TF‑containing microvesicles, contribute to wound healing through regulating a number of cellular properties and functions. TF regulates the cell cycle checkpoints, however the underlying signalling mechanisms have not been determined. Endothelial (human dermal blood endothelial cells and human umbilical vein endothelial cells) and epithelial [human telomerase reverse transcriptase‑human pancreatic nestin‑expressing ductal cells (hTERT‑HPNE) and AsPC‑1] cells were exposed to different concentrations of recombinant TF, and the influence on G1/S checkpoint regulators examined. Short‑term exposure to a lower concentration of TF promoted increased p16^INKa and decreased p21^CIP1/WAF1 expression, together with higher early region 2 binding factor (E2F) transcriptional activity and increased phosphorylation of Thr821/826 within retinoblastoma protein, leading to cell proliferation. The increase in p16^INKa expression was prevented following inhibition of β1‑integrin, or blocking the exosite within TF with AIIB2 and 10H10 antibodies, respectively. Exposure of cells to higher concentrations of TF induced disproportionate increases in p16^INKa and p21^CIP1/WAF1 expression, reduced retinoblastoma protein phosphorylation and E2F activity. Prolonged treatment of the immortalised hTERT‑HPNE cells with recombinant TF, resulted in significant downregulation of p16^INKa protein, which was partially due to reduced mRNA expression, together with increased E2F activity, and cyclin E mRNA expression. Although an increase in the methylation of the p16^INKa promoter was detected, the reduction in p16^INKa protein was concurrent with, and partly attributed to increased p14^ARF expression. TF appears early at the site of trauma, and its concentration is an ideal gauge for determining the extent of cellular damage, initiating clearance and repair. It is hypothesised that the balance of this signal is also dependent on the ability of cells to moderate the TF, and therefore on the level of damage. However, prolonged exposure of cells for example due to inflammation, leads to the dysregulation of the G1/S checkpoint by the tumour suppressors, leading to aberrant growth.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blotting data shown in Fig. 4B on p. 4988 had already appeared in an article written by different authors at different research institutes that had already been published. In addition, it appeared as if some of the control β‑actin protein bands had been re‑used in Fig. 3 on p. 4987, comparing between Fig. 3A and C.  Owing to the fact that the contentious data in the above article 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 14: 4983‑4990, 2016; DOI: 10.3892/mmr.2016.5916].

Long noncoding RNA (lncRNA) PTTG3P has been demonstrated to participate in the development of hepatocellular carcinoma (HCC) by targeting the mRNA PTTG1. The present study aimed to investigate the diagnostic efficacy of serum lncRNA PTTG3P, mRNA PTTG1 and their combination for the diagnosis and prognosis of HCC. A total of 373 participants were enrolled in the present study, including 73 patients with HCC, 100 patients with chronic hepatitis B (CHB), 100 patients with liver cirrhosis (LC) and 100 healthy controls (HCs). The expression levels of serum RNAs were quantified by reverse transcription‑quantitative PCR. The association between serum lncRNA PTTG3P and clinical characteristics was further analyzed. Receiver operating characteristic (ROC) curve and area under curve (AUC) analyses were performed to estimate the diagnostic ability of serum lncRNA PTTG3P, PTTG1 and their combinations with other biomarkers for HCC. The results revealed that the expression levels of lncRNA PTTG3P and mRNA PTTG1 were markedly increased in the serum of patients with HCC and CHB compared with in the serum of HCs. Additionally, the postoperative levels of lncRNA PTTG3P and mRNA PTTG1 were significantly lower than the preoperative concentrations in 36 paired patients with HCC. Spearman's correlation coefficient analysis showed that serum lncRNA PTTG3P was correlated with aspartate transaminase (AST). ROC analysis showed that both lncRNA PTTG3P and mRNA PTTG1 had a significant predictive value for HCC. The AUC values of lncRNA PTTG3P and mRNA PTTG1 alone were 0.636 and 0.634, respectively. Furthermore, combining lncRNA PTTG3P, mRNA PTTG1, α‑fetoprotein (AFP), alanine aminotransferase (ALT), AST, γ‑glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) significantly increased the AUC value. The best performance was the combination of PTTG3P, PTTG1, AFP, ALT, AST, GGT and ALP with an AUC of 0.959, a sensitivity of 90.4% and a specificity of 98.0%. In conclusion, the combination of serum lncRNA PTTG3P, mRNA PTTG1 and AFP appeared to be a noninvasive biomarker with comparatively high specificity and sensitivity for the diagnosis of HCC.

Myocardial infarction (MI) is the leading cause of death worldwide and currently there are limited therapies that can regenerate the lost cardiac cells following MI. To enhance the therapeutic effects of human induced pluripotent stem cell‑derived cardiomyocytes (hiPSC‑CM) transplantation for treatment of MI, the present study sought to increase the pro‑angiogenic effect of hiPSC‑CM by overexpressing a mutated hypoxia‑inducible factor 1‑alpha (HIF‑1α; P402A; P564A) via lentivirus transfection. Morphology and the electrophysiology of the genetically engineered cell were both unchanged. The present study demonstrated that the proangiogenic factors in the conditioned medium of the HIF‑1α‑overexpressing hiPSC‑CM (HIF‑CM) were upregulated and subsequently resulted to the rescue of the tube forming ability and migratory ability of the hypoxia‑injured human umbilical vein endothelial cells. Using a MI mouse model, the present study demonstrated that the transplantation of HIF‑CM greatly improved cardiac function, decreased scar size, promoted the concentration of the proangiogenic factors in circulation and promoted the neovessel formation in mice with MI. In conclusion, HIF‑1α‑overexpressing hiPSC‑CM could increase the angiogenesis of endothelial cells and mediate cardioprotection in mouse following MI.

High myopia and age‑related cataracts are prevalent ocular disorders that compromise visual acuity. The molecular mechanisms underlying these conditions remain largely unclear. Here, microRNA (miRNA or miR) sequencing was performed on aqueous humor samples obtained from individuals with age‑related cataracts and high myopia (AH, n=9), young patients with high myopia (YH, n=9) and a control group of elderly patients with age‑related cataracts, matched in terms of sex and age (AN, n=9). miRNA sequencing and differential expression were performed. Intersecting miRNAs were identified, as well as metabolism‑related genes from MsigDB were intersected with miRNA target genes. Functional enrichment was performed and disease targets predicted using DisGeNET. A protein‑protein interaction network was built with STRING, and hub genes were identified via Cytoscape. GeneMANIA analyzed hub genes, while drug predictions were made using Comparative Toxicogenomics Database. Long non‑coding RNAs and transcription factors were predicted via mirNet and ChEA3. Results were validated by RT‑qPCR. A total of 18 miRNAs were significantly differential expressed between AH and AN group, of which eight were up‑ and 10 were downregulated. A total of 23 miRNAs were significantly differential expressed between the YH and AN group, of which six were up‑ and 17 were downregulated. hsa‑miR‑490‑3p, hsa‑miR‑4423‑3p and hsa‑miR‑4485‑3p may serve as characteristic miRNAs. A total of 289 target genes were predicted. Functional enrichment analysis yielded 169 terms, with 'herpes simplex virus 1 infection' the most significantly enriched. There were 19 metabolism‑associated target genes linked with these miRNAs, suggesting a potential role of metabolic processes in pathogenesis of these conditions. The biosynthetic process of carbohydrate derivatives may serve a key role during the development of high myopia. There were 10 hub genes and Propionyl‑CoA Carboxylase Subunit β could potentially serve as a biomarker. Drugs that could modulate their function were predicted; cyclosporine, tretinoin and acetaminophen may exert a broad influence on these hub genes. Hub gene networks based on the miRNAs were constructed to predict 44 associated long non‑coding RNAs and 98 transcription factors. The present findings offer novel insights into the molecular mechanisms of age‑related cataracts and high myopia and propose potential therapeutic targets.

Schizophrenia, a complex psychiatric disorder, presents with multifaceted symptoms and important challenges in treatment, primarily due to its pathophysiological complexity, which involves oxidative stress and aberrant iron metabolism. Recent insights into ferroptosis, a unique form of iron‑dependent cell death characterized by lipid peroxidation and antioxidant system failures, open new avenues for understanding the neurobiological foundation of schizophrenia. The present review explores the interplay between ferroptosis and schizophrenia, emphasizing the potential contributions of disrupted iron homeostasis and oxidative mechanisms to the pathology and progression of this disease. The emerging evidence linking ferroptosis with the oxidative stress observed in schizophrenia provides a compelling narrative for re‑evaluating current therapeutic strategies and exploring novel interventions targeting these molecular pathways, such as the glutathione peroxidase 4 pathway and the ferroptosis suppressor protein 1 pathway. By integrating recent advances in ferroptosis research, the current review highlights innovative therapeutic potentials, including N‑acetylcysteine, selenium, omega‑3 fatty acids and iron chelation therapy, which could address the limitations of existing treatments and improve clinical outcomes for individuals with schizophrenia.

Liver hepatocellular carcinoma (LIHC) is a prevalent and lethal malignancy with a complex molecular landscape. Fibrosis and ferroptosis are implicated in LIHC progression, yet their roles remain to be elucidated. The present study investigated the expression and prognostic significance of calcitonin receptor (CALCR), a gene that intersects the pathways of fibrosis and ferroptosis, across LIHC and other types of cancer. Data were obtained from The Cancer Genome Atlas and the Molecular Signatures Database. LIHC patients were classified into two clusters based on fibrosis‑related gene expression using ConsensusClusterPlus. Single‑sample gene set enrichment analysis was employed to quantify fibrosis and ferroptosis levels. Correlation, survival and nomogram analyses were performed to assess the prognostic value of CALCR. Additionally, single‑cell RNA sequencing data from the Tumor Immune Single Cell Hub 2 (TISCH2) and pan‑cancer analyses of genomic heterogeneity features were incorporated. The present study also identified a putative regulatory role for CALCR in LIHC cell migration, proliferation and apoptosis. CALCR was identified as a significant prognostic marker for LIHC. Patients with high CALCR expression exhibited shortened overall survival (OS) and disease‑specific survival (DSS). Specifically, the hazard ratios (HRs) for OS and DSS were 1.76 [95% confidence interval (CI): 1.23=2.49) and 1.77 (95% CI: 1.13=2.78], respectively, with corresponding P‑values of 0.002 for OS and 0.013 for DSS. Analyses of immune cell infiltration revealed a more complex immune environment in patients with low CALCR expression, suggesting differential responses to immunotherapy. Furthermore, in HepG‑2 and HuH‑7 cells, small interfering (si)‑CALCR increased apoptosis while reducing proliferation and migration compared with si‑negative control. CALCR serves as a significant prognostic biomarker for LIHC, influencing both molecular pathways and the immune landscape. Its expression is associated with improved survival outcomes and distinct genomic features, positioning it as a potential therapeutic target and predictor of immunotherapy efficacy.

Gastric cancer (GC) is characterized by a high mortality rate (70%) worldwide. Programmed cell death‑1 and its ligand, programmed cell death ligand 1 (PD‑L1), are vital immune checkpoints, which serve a notable role in GC. Solamargine, an extract from traditional Chinese medicine Long Kui, exerts suppressive effects on several types of cancer including cervical, lung and prostate cancer. However, the association between solamargine and PD‑L1 in GC remains unclear. Therefore, the present study aimed to investigate the underlying mechanism of solamargine on GC. Specifically, 5‑ethynyl‑2'‑deoxyuridine and Transwell assays were performed to assess GC cell proliferation, invasion and migration. Additionally, GC cells (HGC‑827 and NCI‑N87) were stimulated with 20 ng/ml recombinant human IL‑6 for 24 h, before the protein expression levels of PD‑L1 were measured using western blot analysis. Furthermore, T cell function was evaluated through incubation of Jurkat T cells with solamargine. The results demonstrated that solamargine could markedly inhibit GC cell proliferation, migration and invasion, by inhibiting STAT3 signaling. In addition, GC cell treatment with solamargine downregulated the expression of PD‑L1. Furthermore, solamargine reversed the IL‑6‑induced PD‑L1 upregulation in GC cells by downregulating STAT3 activity. Additionally, the results demonstrated that solamargine inhibited IL‑6‑induced PD‑L1 upregulation of GC cells. This suggests that solamargine exerted an immunostimulatory activity in GC. In conclusion, the present study indicated that solamargine may inhibit the progression of GC by suppressing STAT3/PD‑L1 signaling. Therefore, treatment with solamargine may serve as novel strategy for the treatment of GC.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell apoptotic data shown in Fig. 3A, the flow cytometric (FCM) data in Fig. 3B on p. 67, and the western blot data shown in Fig. 5 on p. 68 were strikingly similar to data that had either already been submitted for publication elsewhere, or which subsequently appeared in different form in other articles/publications. Moreover, patterns of data featured within certain quadrants of the FCM plots featured in Fig. 5 appeared to be strikingly similiar to other patterns of data when comparing between the quadrants of the FCM plots within this same figure, such that the similarities were difficult to attribute to coincidence. Owing to the fact that the abovementioned data have apparently subsequently appeared in other unrelated articles, and owing to the potentially anomalous presentation of data in the FCM plots in Fig. 5, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on the grounds of an overall 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 12: 63‑70, 2015; DOI: 10.3892/mmr.2015.3395].