Molecular medicine reports最新文献

Atherosclerosis (AS) is a chronic, multifactorial condition strongly associated with the onset and progression of cardiovascular disease, and it remains one of the leading causes of mortality worldwide. Endothelial cell apoptosis is an important event in the initiation and development of AS. MicroRNAs (miRNAs/miRs) have been extensively studied and perform roles at various stages of AS. Among them, miR‑222‑5p has been implicated in the regulation of AS; however, its precise mechanistic involvement remains to be fully elucidated. Therefore, the present study aimed to determine the functional role and underlying mechanism of miR‑222‑5p in AS. To this end, human umbilical vein endothelial cells (HUVECs) were treated with oxidized low‑density lipoprotein (ox‑LDL) to establish an endothelial cell apoptosis model. Reverse transcription‑quantitative polymerase chain reaction was used to assess mRNA and miRNA levels, and transfection efficiency. Cell viability was measured using the Cell Counting Kit‑8 assay and apoptosis was determined by flow cytometry. The protein expression levels of Bax, Bcl‑2 and integrin subunit α5 (ITGA5) were determined by western blotting. The results revealed that ox‑LDL stimulation significantly increased miR‑222‑5p expression in HUVECs. Overexpression of miR‑222‑5p significantly promoted apoptosis, whereas its knockdown reduced apoptosis and improved cell viability. Further analysis identified ITGA5 as a potential downstream target of miR‑222‑5p. In ox‑LDL‑induced apoptosis models, ITGA5 expression was significantly downregulated, and transfection with small interfering RNA targeting ITGA5 (si‑ITGA5) enhanced apoptotic activity. Furthermore, an inverse relationship was observed between ITGA5 and miR‑222‑5p expression. Co‑transfection experiments revealed that si‑ITGA5 partially reversed the anti‑apoptotic effects of the miR‑222‑5p inhibitor. In summary, the present study demonstrated that miR‑222‑5p may regulate endothelial cell apoptosis by targeting ITGA5, potentially contributing to AS progression.

Interstitial lung diseases (ILDs) include various lung parenchymal disorders characterized by inflammation and fibrosis of the lung tissue, leading to progressive dyspnea and respiratory failure. Clinical evidence has suggested an association between human parvovirus B19 (B19V) infection and the progression of ILD and pulmonary fibrosis, but the mechanisms involved remain unclear. The present study screened 86 patients with connective tissue disease (CTD) and reported that B19V infection was significantly more prevalent among those with ILD than among those without (P<0.001). To investigate the potential underlying mechanisms, a bleomycin (BLM)‑treated mouse model was employed to assess the effect of B19V nonstructural protein 1 (NS1) on pulmonary fibrosis. Mice treated with BLM or BLM + NS1 exhibited markedly higher fibrosis scores, hydroxyproline content, and higher levels of transforming growth factor‑β and collagen I. Treatment with nintedanib attenuated fibrosis in both groups; however, lung fibrosis remained more pronounced in the BLM + NS1 group than in the BLM group. Furthermore, the levels of neutrophil‑associated markers, including citrullinated histone H3 and myeloperoxidase, as well as inflammasome‑related factors, such as IL‑18 and IL‑17A, were markedly elevated in lung tissues from both groups, with the highest levels observed in the BLM + NS1 group. These findings suggested that B19‑NS1 may exacerbate fibrosis in patients with ILD by increasing neutrophil‑driven responses and inflammasome activation, highlighting a need for nintedanib therapies to more effectively address B19V‑associated pulmonary fibrosis.

Prostate cancer (PCa) ranks among the most prevalent malignancies among men worldwide, emphasizing the need for innovative therapeutic strategies. Studies have suggested that the gut microbiota may markedly influence PCa pathogenesis through mechanisms such as immunomodulation and metabolic regulation. The present review systematically examined the composition and diversity of the gut microbiota, highlighted clinical evidence linking microbial dysbiosis to PCa risk and examined discrepancies in existing research. Additionally, it explored the therapeutic potential of microbiota modulation, through the use of probiotics and dietary interventions, in enhancing treatment responses. Despite emerging insights, challenges persist, including methodological variations and patient heterogeneity. The present review highlighted the need for further research to elucidate the role of the gut microbiota and support the development of personalized approaches for PCa management. The novelty of this work lay in its comprehensive synthesis of current evidence on the role of the gut microbiota in PCa, identification of gaps in existing research and proposal of future directions to advance our understanding of this emerging field.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell morphological data shown in Fig. 3 on p. 1106 and the flow cytometric data shown in Fig. 4 on p. 1107 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been accepted for publication elsewhere 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 15: 1103‑1108, 2017; DOI: 10.3892/mmr.2017.6136].

Hyperoside (Hyp), a naturally occurring flavonol glycoside derived from Crataegus, otherwise known as hawthorn, possesses potent antioxidant properties and has demonstrated therapeutic potential in various oxidative stress‑related diseases, including osteoporosis (OP). However, the precise molecular mechanisms underlying the anti‑osteoporotic effects of Hyp remain to be fully elucidated. The present study aimed to evaluate the therapeutic efficacy of Hyp against OP and to elucidate its underlying mechanisms. An osteoporotic mouse model was established via bilateral ovariectomy (OVX) to assess the in vivo efficacy of Hyp. Network pharmacology was employed to predict the potential therapeutic targets of Hyp in OP. In vitro experiments using bone marrow mesenchymal stem cells (BMSCs) were performed to validate the findings. Techniques including alkaline phosphatase staining, Alizarin red S staining, reverse transcription‑quantitative PCR and western blotting were used to assess osteogenic differentiation and molecular signaling pathways. Micro‑CT analysis revealed that Hyp significantly ameliorated OVX‑induced bone loss in mice. Network pharmacology identified the PI3K/AKT signaling pathway as a potential key target. In vitro, Hyp significantly reduced H2O2‑induced oxidative stress in BMSCs and promoted their osteogenic differentiation. Mechanistically, Hyp was found to activate the PI3K/AKT signaling pathway, suggesting its notable role in mediating the antioxidant and osteoinductive effects of Hyp. Summarily, Hyp may effectively alleviate OVX‑induced OP in mice, potentially by mitigating oxidative stress and promoting osteogenesis via activation of the PI3K/AKT signaling pathway. These findings provide novel insights into the therapeutic mechanism of Hyp and support its potential as a candidate agent for OP treatment.

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 Figs. 2D and 4D, and western blot data shown in Fig. 5A, were strikingly similar to data that had already been published previously in articles submitted to different journals that were written by different authors at different research institutes, a few of which have been retracted. 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 19: 1491‑1500, 2019; DOI: 10.3892/mmr.2018.9775].

Chronic kidney disease (CKD) progression is driven by a harmful interplay between impaired mitophagy and sustained oxidative stress. Under normal conditions, mitophagy serves as a protective mechanism by removing damaged mitochondria and limiting the production of reactive oxygen species. However, in CKD, a self‑reinforcing cycle of mitochondrial dysfunction, defective mitophagy oxidative stress, and inflammation occurs, which promotes fibrosis. The present review examines the molecular mechanisms governing mitophagy, with a specific focus on the regulatory roles of core signaling pathways, namely the PTEN‑induced kinase l/Parkin, BCL2 interacting protein 3/Nip3‑like protein X and FUN14 domain‑containing protein l pathways, and how their disruption contributes to CKD. The mechanistic crosstalk between mitophagy and oxidative stress is highlighted as a central pathogenic axis in CKD progression. In addition, emerging therapeutic strategies that aim to restore mitophagy and enhance antioxidant capacity are discussed, suggesting new strategies for targeted CKD treatment.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the TUNEL assay experiments shown in Fig. 2E on p. 5, the Merge panels for the shFLVCR1‑AS1 experiments shown for the Caco‑2 and SW480 cell lines appeared to have been inserted into this figure the wrong way around. The authors were contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper; however, up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of 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 23: 139, 2021; DOI: 10.3892/mmr.2020.11778].

As the first functional organ to form during vertebrate embryogenesis, the heart exhibits heightened susceptibility to developmental toxicity. Epigenetic regulatory mechanisms, including DNA methylation, histone modifications, non‑coding RNAs, N6‑methyladenosine methylation and chromatin accessibility alterations, mediate cardiac developmental toxicity induced by exogenous compounds including environmental chemicals and pharmaceuticals. The present review comprehensively summarizes the current understanding of the molecular mechanisms through which these compounds exert cardiac developmental toxicity through epigenetic regulation. An in‑depth analysis of research progress and technical challenges across diverse epigenetic pathways is provided. By summarizing recent evidence, the present review proposes candidate epigenetic biomarkers for cardiac developmental toxicity monitoring and explores potential intervention strategies targeting these pathways. Future research should prioritize multi‑omics integration technologies and clinical translation system development. These advances are anticipated to foster innovation in both mechanistic research and preventive strategy development for cardiac developmental toxicity.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that, within the left‑hand and centre data panels of Fig. 6 on p. 5735, apparent anomalies were identifiable, including unexpectedly similar‑looking cells and repeated patternings of these cells in terms of their layout/arrangement, albeit with inversions of the cells in certain cases. In addition, it was noted that some of the data featured in Table I and in Fig. 4B were strikingly similar to data that had previously appeared in a paper published in the journal Cell Biochemistry and Biophysics that was written by different authors at different research institutes. After having conducted an independent investigation of this paper in the Editorial Office, the Editor of Molecular Medicine Reports has determined that it should be retracted from the Journal on account of a lack of confidence in the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [Molecular Medicine Reports 12: 5730‑5736, 2015; DOI: 10.3892/mmr.2015.4169].