Molecular medicine reports最新文献

The present research explored the contributions of signal transducer and activator of transcription 1 (STAT1) and tubulin β4A (TUBB4A) in melanoma pathogenesis, focusing on their roles in modulating cellular proliferation, motility and apoptotic pathways. The goal of the study was to establish foundational evidence of the role of these proteins in melanoma for the development of precision therapeutic interventions. Gene silencing approaches were utilized to suppress STAT1 expression, while TUBB4A overexpression was achieved both in vitro and in a murine xenograft model. Cellular proliferation was evaluated via Cell Counting Kit‑8 and colony formation assay, whereas migration capacity was assessed using Transwell migration assays. Apoptotic activity was quantified by flow cytometry using Annexin V‑FITC and PI staining. Western blot analysis was performed to measure the protein expression levels of STAT1 and TUBB4A. STAT1 downregulation led to impaired proliferation and motility in A375 and RPMI‑7951 melanoma cell lines, concomitant with increased apoptotic rates. These phenotypic changes were partially reversed following TUBB4A overexpression. In vivo experiments demonstrated significantly smaller tumor volumes in STAT1 knockdown xenografts, although TUBB4A overexpression partially restored neoplastic growth. STAT1 drove melanoma progression by upregulating TUBB4A, which acted as a downstream signaling mediator. The ability of TUBB4A to counteract STAT1 inhibition effects suggested that targeting this regulatory axis represents a potential therapeutic strategy. The findings of the present study contributed novel mechanistic insights that may facilitate the development of innovative melanoma treatment modalities.

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. 5208 were strikingly similar to data that had appeared previously in other papers written by different authors at different research institutes. 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 19: 5203-5210, 2019; DOI: 10.3892/mmr.2019.10186].

Low back pain (LBP) is a leading cause of productivity loss worldwide and a major contributor to disability, imposing an economic burden on society. Intervertebral disc degeneration (IVDD) as a principal pathological driver of LBP remains a formidable therapeutic challenge, given that existing conservative and surgical interventions frequently fall short of achieving long‑term efficacy or halting disease progression. Advancements in molecular biology have revealed that circular RNAs (circRNAs) play a pivotal role in the intricate gene regulatory networks governing IVDD. The most extensively studied function of circRNAs is their ability to act as microRNA sponges. In addition, they participate in protein interactions, regulate gene transcription and serve as templates for protein translation. The present review provided a comprehensive overview of the current understanding of circRNA characteristics and functions, elucidated their involvement in IVDD pathogenesis and examined the therapeutic potential of emerging biomaterials for IVDD treatment. By consolidating existing research, the aim of this review was to offer theoretical foundations for innovative therapeutic strategies targeting IVDD.

Diffuse alveolar hemorrhage (DAH) is a rare life‑threatening pulmonary disorder in children, characterized by cough, hemoptysis and dyspnea. The pathogenesis is not fully understood, posing notable challenges for clinical diagnosis and management. Recent advances have gradually revealed potential etiologies and associated immune mechanisms, driving the development and application of novel therapies. The present review aimed to summarize the current understanding of the etiology, diagnostic approaches and therapeutic strategies for pediatric DAH, with a focus on the emerging role of the CD20 monoclonal antibody rituximab, and highlighted clinical evidence supporting its use in immune‑related DAH. The present review aimed to provide a foundation for further research and optimize clinical decision‑making.

The present study aimed to elucidate abnormal proliferation of colonic epithelial cells in type 2 diabetes mellitus (T2DM), a potential early step in colonic carcinoma development. Analysis of normal adjacent colonic epithelium obtained from colonic carcinoma surgeries showed an increased proliferative index among patients with T2DM. In vitro, high‑glucose medium mimicking diabetic conditions enhanced the proliferation of NCM460 cells, a normal human colon mucosal epithelial cell line. To identify dysregulated N6‑methyladenosine modifiers, the present study analyzed RNA sequencing datasets from the GEO database and identified an upregulated expression of insulin‑like growth factor 2 mRNA binding protein 2 (IGF2BP2) in the colonic epithelium of patients with T2DM, which was subsequently confirmed in the clinical samples and in vitro. IGF2BP2 knockdown inhibited the high glucose‑induced proliferation. Further bioinformatic evidence suggested midkine (MDK) as a potential target of IGF2BP2. MDK upregulation was confirmed in colonic epithelium under T2DM conditions, and its knockdown also inhibited high glucose‑induced proliferation. Overexpression of MDK partially prevented the anti‑proliferative effect of IGF2BP2 knockdown. Mechanistically, IGF2BP2 knockdown reduced MDK mRNA stability. RNA immunoprecipitation confirmed that IGF2BP2 bound to MDK mRNA, and this binding was significantly diminished upon mutation of the top three predicted N6‑methyladenosine modification sites in MDK. These findings suggested that the IGF2BP2/MDK axis contributed to abnormal colonic epithelial proliferation under T2DM conditions and may represent a potential therapeutic target to reduce carcinoma risk in patients with diabetes.

Cardiovascular diseases (CVDs) remain the primary cause of death worldwide. Exploring novel therapeutic targets is important for defining future research directions in cardiovascular medicine. Considering the notable role of cell death in disease pathogenesis, targeting disulfidptosis may represent a valuable therapeutic strategy for CVDs. However, current research increasingly centers on cancer, and the role of disulfidptosis in the cardiovascular field remains insufficiently explored. Accordingly, the present review examines the mechanisms of disulfidptosis across different cardiac cell types: Cardiomyocytes, vascular smooth muscle cells, endothelial cells and fibroblasts. Furthermore, the review discusses existing evidence for disulfidptosis in CVDs and potential intervention strategies, aiming to provide new perspectives for preventing and treating CVDs.

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].

Myocardial ischemia‑reperfusion injury (MIRI) can trigger inflammatory responses and cause pyroptosis. Puerarin (Pue), as a traditional medicine, exhibits potential value in cardiac protection. However, the mechanism by which Pue regulates pyroptosis in MIRI remains to be fully elucidated. The present study aimed to explore the cardioprotective effects of Pue against MIRI and reveal the underlying mechanisms of these effects. Sprague‑Dawley rats were used to establish in vivo models of MIRI, while H9C2 rat embryonic cardiomyocytes were employed as in vitro models. Echocardiography was performed to measure cardiac function. Triphenyltetrazolium chloride/Evans blue staining, hematoxylin‑eosin staining, Masson's trichrome staining and immunohistochemistry were employed to assess the pharmacodynamic effects of Pue. The expression of molecules related to pyroptosis, such as nuclear factor E2‑related factor 2 (NRF2) and heme oxygenase‑1 (HO‑1) were detected by immunofluorescence, Hoechst 33342/PI staining, reverse transcription‑quantitative PCR and western blot analyses. The results of the present study showed that Pue pretreatment reduced the area of myocardial infarction and decreased the expression of pyroptosis‑related molecules. Additionally, Pue was shown to reverse H2O2‑induced mitochondrial dysfunction in cardiomyocytes and inhibit nucleotide‑binding oligomerization domain‑like receptor family pyrin domain‑containing 3 (NLRP3)/caspase‑1/gasdermin D (GSDMD)‑mediated pyroptosis. Pue was also shown to stimulate the nuclear translocation of NRF2 and increase the expression of HO‑1. Furthermore, Pue further demonstrated its anti‑pyroptotic effects by activating the NRF2/HO‑1 pathway. The present study revealed that Pue can protect injured myocardium after MIRI by inhibiting NLRP3/caspase‑1/GSDMD‑mediated pyroptosis. The mechanism of action for these cardioprotective effects relied upon downregulation of the NRF2/HO‑1 signaling pathway. The findings of the present study provided a novel strategy for the clinical application of puerarin in the treatment of MIRI.

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].

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.