Molecular medicine reports最新文献

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that there was a possible duplication of cell‑cycle analysis data shown in Fig. 4A on p. 4977. 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 17: 4973‑4980, 2018; DOI: 10.3892/mmr.2018.8509].

Neuroblastoma (NB), the most common extracranial solid tumor in children, remains challenging to treat due to limited therapeutic efficacy and poor prognosis. Emerging evidence highlights the critical roles of endoplasmic reticulum (ER) stress and autophagy in cancer progression. The present study investigated the therapeutic potential of melatonin in neuroblastoma and its underlying mechanisms. Using Neuro‑2a (N2a) cells, it demonstrated that melatonin alleviated ER stress by upregulating ER chaperones glucose‑regulated protein (GRP)78 and GRP94 and the pro‑apoptotic protein CHOP, while enhancing autophagic activity. Western blotting revealed increased LC3‑II/I ratios, elevated autophagy‑related protein 5 and Beclin1 levels, and reduced p62 expression, indicating autophagy induction. Immunofluorescence and transmission electron microscopy confirmed the dose‑dependent accumulation of autophagosomes. ER stress inhibitor 4‑phenylbutyric acid attenuated melatonin‑induced autophagy, linking ER stress relief to autophagic activation. Mechanistically, melatonin upregulated p21‑activated kinase 2 (Pak2), which suppressed mTOR phosphorylation and activated unc‑51‑like kinase 1, thereby modulating the AMP‑activated protein kinase (AMPK) pathway. Pak2 overexpression amplified melatonin's ER stress‑alleviating effects, whereas Pak2 knockdown or AMPK inhibition diminished its efficacy. These findings established that melatonin suppresses neuroblastoma growth by mitigating Pak2‑mediated ER stress to induce cytotoxic autophagy. The present study provided novel insights into melatonin as a promising therapeutic agent for neuroblastoma, warranting further exploration in preclinical models and clinical trials.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that western blot data appeared to have been assembled incorrectly in Fig. 4A on p. 6709. In this case, there was an apparent inversion of the p‑PI3K bands, and inclusion of one of these bands as a unique band (upside down) for the Control experiment in the p‑Akt row of data, purportedly showing the results of a different set of experiments. 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 17: 6705-6710, 2018; DOI: 10.3892/mmr.2018.8678].

Aberrant expression of microRNAs (miRNAs) has been closely linked to the progression of rheumatoid arthritis (RA). The present study explored the potential role of miR‑369‑3p in regulating immune‑driven inflammation and bone degradation in RA through the spectrin β, non‑erythrocytic 1 (SPTBN1)/Wnt/β‑catenin signaling cascade. To test this, synthetic mimics and inhibitors of miR‑369‑3p were generated and transfected into RA fibroblast‑like synoviocytes (RA‑FLSs). A pathological model was established by co‑culturing RA‑FLSs with peripheral blood mononuclear cells (PBMCs). The influence of miR‑369‑3p overexpression or suppression on RA‑FLS behavior was assessed in terms of cell survival, cell cycle distribution, proliferation and migratory capacity. Bioinformatics predictions together with luciferase reporter assays confirmed the direct interaction between miR‑369‑3p and SPTBN1. Expression levels of inflammatory cytokines, bone metabolism markers and matrix metalloproteinases were measured by ELISA, while reverse transcription‑quantitative PCR and western blotting were employed to evaluate alterations in the miR‑369‑3p/SPTBN1/Wnt/β‑catenin pathway. The results showed that miR‑369‑3p expression was markedly reduced in the PBMC‑induced RA‑FLS model. Transfection with miR‑369‑3p mimics suppressed the viability and proliferation of RA‑FLS and decreased the expression of SPTBN1, Wnt ligands and β‑catenin mRNA. By comparison, inhibition of miR‑369‑3p produced opposite effects. ELISA findings demonstrated that the miR‑369‑3p/SPTBN1 pathway modulated critical inflammatory and bone‑related markers, which were consistently confirmed across replicate experiments. These results suggested that miR‑369‑3p regulates RA pathology by targeting the SPTBN1/Wnt/β‑catenin pathway, attenuating inflammatory responses and limiting bone destruction in RA.

Myocardial ischemia/reperfusion injury (MIRI) is a challenging cardiovascular disease. Mepivacaine, a common local anesthetic, exacerbates myocardial injury during ischemia‑reperfusion (IR). Understanding the underlying mechanisms of MIRI and potential therapeutic targets is important to treat this disease. In the present study, differentially expressed genes (DEGs) from the GSE19339 dataset were identified and analyzed. The expression of calcium voltage‑gated channel auxiliary subunit β1 (CACNB1) was measured in myocardial infarction samples and the effects of different doses of mepivacaine on cell cycle progression, apoptosis, cell viability, inflammatory response and oxidative stress were evaluated in H9c2 cells. Hypoxia‑reoxygenation (H/R) treatment simulated MIRI, highlighting the role of CACNB1 in mepivacaine‑induced cellular inflammation and injury. The present study identified 2,396 upregulated and 1,230 downregulated DEGs enriched in pathways such as inflammatory response and chemokine signaling. Mepivacaine induced apoptosis, G₁ phase arrest and increased oxidative stress markers, including elevated ROS and MDA levels together with decreased SOD activity, as well as inflammatory cytokines (TNF‑α, IL‑1β and IL‑6), in a dose‑dependent manner in H9c2 cells. CACNB1 knockdown reduced mepivacaine‑ and H/R‑induced damage, inhibiting inflammation and apoptosis via the CACNB1/NOD‑like receptor protein 3 (NLRP3)/Nuclear factor erythroid 2‑related factor 2 (Nrf2) axis. Furthermore, CACNB1 knockdown enhanced Nrf2 nuclear translocation, indicating a stress response mechanism. Mepivacaine exacerbated MIRI by inducing apoptosis, G₁ phase arrest, oxidative stress and inflammation in H9c2 cells. CACNB1 knockdown reduced these effects. Targeting the CACNB1/NLRP3/Nrf2 axis may be a potential strategy for mitigating myocardial injury caused by mepivacaine and IR.

Myocardial hypertrophy (MH) represents an early pathological manifestation that progresses to severe cardiovascular disease (CVD), and its reversal is important for preventing and treating heart failure. Dysregulated expression of ATP‑binding cassette subfamily C member 9 (ABCC9) has been associated with complex CVD pathogenesis, although its precise mechanistic role remains ambiguous. The present study was designed to investigate the protective effects of ABCC9 knockdown against isoproterenol (ISO)‑induced MH and elucidate its underlying molecular mechanisms. AC16 cardiomyocytes were treated with ISO to establish an MH model, in which ABCC9 protein expression was significantly elevated. Fluorescence staining of cardiomyocyte surface area and quantification of MH‑related biomarkers, including atrial natriuretic peptide, brain natriuretic peptide and β‑myosin heavy chain, demonstrated that ABCC9 knockdown effectively attenuated MH and improved cardiac function. Furthermore, western blot analysis and flow cytometry revealed that ABCC9 knockdown not only decreased cardiomyocyte apoptosis but also reduced oxidative stress, as indicated by lower reactive oxygen species levels. Mechanistically, western blotting and mitochondrial membrane potential assays showed that ABCC9 knockdown inhibited the phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway and improved mitochondrial function. Notably, these protective effects were diminished by treatment with the PI3K/AKT activator 740Y‑P. These findings collectively suggest that ABCC9 knockdown protects against MH by inhibiting the PI3K/AKT signaling pathway, thereby alleviating mitochondrial dysfunction and reducing apoptosis and oxidative stress, positioning ABCC9 as a potential therapeutic target for MH treatment.

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].

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.

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.

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.