Molecular medicine reports最新文献

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the cell migration and invasion assay experiments shown in Fig. 2 on p. 6322, the 'HeLa/miR‑378 inhibitor' panels in Fig. 2B and C appeared to contain overlapping sections of data, such that these data panels were apparently derived from the same original source to show the results of purportedly different experiments. The authors have re‑examined their original data, and realize that Fig. 2C was inadvertently assembled incorrectly. The revised version of Fig. 2, now containing the correct data for the 'HeLa/miR‑378 inhibitor' experiment in Fig. 2C, is shown on the next page. Note that this error 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 17: 6319‑6326, 2018; DOI: 10.3892/mmr.2018.8645].

Diabetic wounds represent a significant complication of diabetes and present a substantial challenge to global public health. Macrophages are crucial effector cells that play a pivotal role in the pathogenesis of diabetic wounds, through their polarization into distinct functional phenotypes. The field of epigenetics has emerged as a rapidly advancing research area, as this phenomenon has the potential to markedly affect gene expression, cellular differentiation, tissue development and susceptibility to disease. Understanding epigenetic mechanisms is crucial to further exploring disease pathogenesis. A growing body of scientific evidence has highlighted the pivotal role of epigenetics in the regulation of macrophage phenotypes. Various epigenetic mechanisms, such as DNA methylation, histone modification and non‑coding RNAs, are involved in the modulation of macrophage phenotype differentiation in response to the various environmental stimuli present in diabetic wounds. The present review provided an overview of the various changes that take place in macrophage phenotypes and functions within diabetic wounds and discussed the emerging role of epigenetic modifications in terms of regulating macrophage plasticity in diabetic wounds. It is hoped that this synthesis of information will facilitate the elucidation of diabetic wound pathogenesis and the identification of potential therapeutic targets.

The nuclear receptor subfamily 4 group A member 1 (NR4A1) gene plays a crucial role in both osteoporosis and adipogenesis. The present study investigated the mechanisms by which NR4A1 influences osteoblastogenesis and adipogenesis in human bone marrow‑derived mesenchymal stem cells (BMD‑MSCs). NR4A1 was overexpressed or knocked down in mouse MC3T3‑E1 osteoblast cells and 3T3‑L1 adipocyte cells, as well as in PCS‑500‑012, a BMD‑MSC line. The alkaline phosphatase (ALP) assay and Alizarin Red S staining were performed using MC3T3‑E1 and BMD‑MSCs to assess ALP activity and mineralization, while Oil Red O staining was used to assess the lipid content in 3T3‑L1 cells and BMD‑MSCs. Total RNA was isolated from control, NR4A1‑overexpressing and NR4A1 small interfering RNA (siRNA; siNR4A1)‑treated BMD‑MSCs. RNA sequencing (RNA‑seq) was performed to identify differentially expressed genes, followed by ingenuity pathway analysis (IPA) to determine the role of NR4A1 in osteoblastogenesis and adipogenesis. NR4A1 or Nr4a1 knockdown tended to increase ALP activity and significantly increased calcification in BMD‑MSCs (P<0.005) and MC3T3‑E1 cells (P<0.005), respectively. By contrast, NR4A1 or Nr4a1 overexpression significantly decreased ALP activity and calcification. NR4A1 or Nr4a1 knockdown and overexpression significantly decreased and increased adipogenesis, respectively, in BMD‑MSCs (P<0.005 and <0.05, respectively) and 3T3‑L1 cells (P<0.005 in both). Treatments of BMD‑MSCs with an NR4A1 antagonist, 1,1‑bis(3'‑indolyl)‑1‑(p‑hydroxyphenyl) methane and siNR4A1 showed similar results. RNA‑seq and IPA in control, NR4A1 knockdown and NR4A1 overexpressing cells indicated that Notch signaling mediated the effects of NR4A1 in osteoblastogenesis and adipogenesis. Expression of mastermind‑like transcriptional coactivator 3 was reduced in the Notch signaling pathway in cells treated with siNR4A1. In conclusion, NR4A1 suppressed osteoblastogenesis and promotes adipogenesis in human BMD‑MSCs. The present study also suggested that NR4A1 plays a role in the progression of osteoporosis and adipogenesis by modulating the Notch signaling cascade.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that one of the data panels in Fig. 3A on p. 6, showing how carnosol inhibits RANKL-induced osteoclastogenesis in the early stage of differentiation,  was strikingly similar to data that had already been submitted for publication in another article in the journal Annals of Translational Medicine written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [26: 225, 2022; DOI: 10.3892/mmr.2022.12741].

The present study aimed to investigate the role of microRNA (miR)‑221‑3p in endothelial progenitor cells (EPCs) treated with lipoprotein(a) [LP(a)]. EPCs were identified using immunofluorescence assays and miR‑221‑3p levels were measured using reverse transcription‑quantitative PCR. EPC migration was detected using Transwell assays, proliferation was measured by staining with 5‑ethynyl‑2'‑deoxyuridine and adhesion was assessed by microscopy. Flow cytometry was used to measure apoptosis and protein expression was detected using western blotting. A dual‑luciferase reporter assay was used to confirm the target interactions. The proliferation, migration, adhesion and angiogenesis of EPCs were decreased, and apoptosis was increased after treatment with LP(a). These effects were weakened by transfection with miR‑221‑3p inhibitor. The negative effects of LP(a) on EPCs were also weakened by overexpression of silent information regulator 1 (SIRT1). Inhibition of the RAF/MEK/ERK signaling pathway blocked the effects of SIRT1 overexpression. In conclusion, miR‑221‑3p inhibitor transfection activated the RAF/MEK/ERK signaling pathway through SIRT1, promoted the proliferation, migration, adhesion and angiogenesis of EPCs, and reduced apoptosis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease whose etiology is not fully understood. Defective peripheral immune tolerance and subsequent mis‑differentiation and aberrant infiltration of synovium by various immune cells, especially helper T (Th) cells, play an important role in the development of RA. There are significant sex differences in RA, but the results of studies on the effects of sex hormones on RA have been difficult to standardize and hormone replacement therapy has been limited by the potential for serious side effects. Existing research has amply demonstrated that cellular immune responses are largely determined by sex and that sex hormones play a key role in Th cell responses. Based on the aforementioned background and the plasticity of Th cells, it is reasonable to hypothesize that the action of sex hormones on Th cells will hopefully become a therapeutic target for RA. The present review discussed the role of various Th cell subsets in the pathogenesis of RA and also explored the role of sex hormones on the phenotype and function of these aberrantly regulated immune cells in RA as well as other pathologic effects on RA.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric analysis data shown in Fig. 4B on p. 7834 were strikingly similar to data that had already been submitted for publication in different form in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication 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 12: 7830‑7836, 2015; DOI: 10.3892/mmr.2015.4455].

The present study aimed to investigate the effect of swimming training on the angiogenesis of endothelial progenitor cells (EPCs) in type 2 diabetes mellitus (T2DM) rats by upregulating the insulin‑like growth factor 1 (IGF1) expression and to reveal its potential mechanism of action. Male Sprague‑Dawley rats were divided into the Control, Model, Model train, Model train + short interfering (si)‑NC and Model train + si‑IGF1 groups. Serum glucose levels were measured using the oral glucose tolerance test. EPCs were isolated from the bone marrow cavity and identified through morphological observation and immunofluorescence staining. The expression of IGF‑1 mRNA in rat serum and EPCs was analyzed by reverse transcription‑quantitative PCR. The fasting insulin levels in serum were assessed by ELISA. Cell Counting Kit‑8, scratch assay and tube formation assay were used to determine the cell viability, migration and tube formation of rat EPCs, and western blotting was employed to measure the expression levels of IGF1, phosphoinositide 3‑kinase (PI3K), phosphorylated‑PI3K, protein kinase B (AKT) and phosphorylated‑AKT. The present study demonstrated that swimming training significantly decreased the glucose levels and homeostatic model assessment of insulin resistance scores, but increased the fasting insulin levels and IGF1 mRNA expression. Microscopic observation and immunofluorescence identification suggested that EPCs were successfully isolated. In addition, swimming training markedly elevated the levels of IGF1 and promoted cell viability, migration and tube formation in rat EPCs. Furthermore, IGF1 knockdown experiments indicated that swimming training might play a regulatory role by elevating the IGF1 expression to activate the PI3K/AKT pathway. Overall, swimming training promoted the angiogenesis of EPCs in T2DM rats and its potential mechanism may be related to the upregulation of IGF1 expression and the activation of the PI3K/AKT pathway.

Following the publication of this article, a concerned reader drew to the Editor's attention that the experimental design of the western blot assay experiments portrayed in Fig. 5A on p. 7804, and the overall organization of this figure, may have been flawed, as mitochondrial and cytosolic proteins were featured in the figure with only one set of supporting control western blot data; in this scenario, the proteins would necessarily have needed to have been obtained from two separate cell samples in different experiments, and blotted on to separate gels. Moreover, there was also a concern that certain of the gels featured possible breaks in their continuity/splicing events, such that the protein bands in the figure were not shown consecutively, as they would have appeared, in the affected slices. After having conducted an internal investigation, the Editor of Molecular Medicine Reports agrees with the reader that there were anomalies associated with the presentation of Fig. 5. Therefore, on the grounds of a lack of confidence in the presented data, the Editor has decided that the article should be retracted from the publication. 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, and we also thank the reader for bringing this matter to our attention. [Molecular Medicine Reports 17: 7797‑7806, 2018; DOI: 10.3892/mmr.2018.8823].

Germ cell tumors (GCTs) constitute diverse neoplasms arising in the gonads or extragonadal locations. Testicular GCTs (TGCTs) are the predominant solid tumors in adolescents and young men. Despite cisplatin serving as the primary therapeutic intervention for TGCTs, 10‑20% of patients with advanced disease demonstrate resistance to cisplatin‑based chemotherapy, and epithelial‑mesenchymal transition (EMT) is a potential contributor to this resistance. EMT is regulated by various factors, including the snail family transcriptional repressor 2 (SLUG) transcriptional factor, and, to the best of our knowledge, remains unexplored within TGCTs. Therefore, the present study investigated the EMT transcription factor SLUG in TGCTs. In silico analyses were performed to investigate the expression of EMT markers in TGCTs. In addition, a cisplatin‑resistant model for TGCTs was developed using the NTERA‑2 cell line, and a mouse model was also established. Subsequently, EMT was assessed both in vitro and in vivo within the cisplatin‑resistant models using quantitative PCR and western blot analyses. The results of the in silico analysis showed that the different histologies exhibited distinct expression profiles for EMT markers. Seminomas exhibited a lower expression of EMT markers, whereas embryonal carcinomas and mixed GCT demonstrated high expression. Notably, patients with lower SLUG expression had longer median progression‑free survival (46.4 months vs. 28.0 months, P=0.022). In the in vitro analysis, EMT‑associated genes [fibronectin; vimentin (VIM); actin, α2, smooth muscle; collagen type I α1; transforming growth factor‑β1; and SLUG] were upregulated in the cisplatin‑resistant NTERA‑2 (NTERA‑2R) cell line after 72 h of cisplatin treatment. Consistent with this finding, the NTERA‑2R mouse model demonstrated a significant upregulation in the expression levels of VIM and SLUG. In conclusion, the present findings suggested that SLUG may serve a crucial role in connecting EMT with the development of cisplatin resistance, and targeting SLUG may be a putative therapeutic strategy to mitigate cisplatin resistance.