International journal of molecular medicine最新文献

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blot data shown in Fig. 8A and two panels of the Transwell assay data shown in Fig. 5B were strikingly similar to data that subsequently appeared in a pair of other publications. In addition, in Fig. 1C, the data panels shown for the KYSE150 and EC9706 cell lines, and also for the ECA‑109 and HET‑1A cell lines, were found to be overlapping, such that data which were intended to have shown the results from four cell lines appeared to have been derived from only two cell lines; in Fig. 2E, the same image was apparently included for the 'Control' colony formation assay experiments for the two different cell lines investigated (ECA‑109 and KYSE150); and possible anomalies were identified with the western blot data in Fig. 3C.  After having performed an independent review of the data in the Editorial Office, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal on account of a 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. [International Journal of Molecular Medicine 43: 1817‑1829, 2019; DOI: 10.3892/ijmm.2019.4107].

Structural birth defects (SBDs) represent a major subset of congenital malformations arising from abnormalities during organogenesis and subsequent tissue morphogenesis. The triad of congenital heart defects (CHDs), orofacial clefts (OFCs) and neural tube defects (NTDs) dominates the global epidemiology of SBDs, collectively contributing to considerable neonatal mortality while imposing profound clinical and socioeconomic burdens. Conventional genetic screening approaches, such as karyotype and non‑invasive prenatal testing, remain limited in their capacity to decipher the complex genomic factors underlying these SBDs. The advent of advanced genomic technologies (including chromosomal microarray analysis and next‑generation sequencing) and integrated genomic analysis methods [such as copy number variation analysis, single nucleotide variation/insertion and deletion analysis and genome‑wide association studies (GWAS)] has enhanced the capacity to identify pathogenic genetic factors, thereby transforming the mode of prenatal diagnosis and genetic counseling. The application of these technologies, by virtue of more accurate diagnosis and finer disease classification, not only provides a more comprehensive basis for assessing disease severity and prognosis in clinical decision‑making but also offers support for implementing targeted intervention and treatment. The present review systematically evaluates state‑of‑the‑art genomic methodologies and computational approaches for detecting genomic aberrations in CHDs, OFCs and NTDs, and integrates insights from GWAS to elucidate the underlying genetic architecture, contributing to achieving precise predictive modeling and targeted therapeutic innovation for SBDs.

Cognitive impairment encompasses a spectrum of neurological deficits affecting memory, attention, executive function and other higher‑order cognitive processes. Increasing attention has been paid to modifiable lifestyle factors that influence its onset and progression. Among these, chronic high‑fat diet (HFD) consumption has emerged as a significant and potentially reversible risk factor for cognitive decline. Both epidemiological and experimental studies have consistently linked HFD‑particularly diets rich in saturated fatty acids‑to impairments in memory, attention and executive functions. Mechanistically, HFD induces neuroinflammation, oxidative stress, insulin resistance and gut microbiota dysbiosis, which collectively disrupt synaptic plasticity and neuronal survival. Individual susceptibility factors such as age, sex and the presence of the apolipoprotein E ε4 allele may further exacerbate these pathological effects. This review also highlights promising intervention strategies, including adherence to Mediterranean or Dietary Approaches to Stop Hypertension dietary patterns, regular physical exercise, pharmacological approaches and gut microbiota modulation. A comprehensive understanding of these multifactorial pathways is essential for developing targeted preventive and therapeutic interventions to mitigate HFD‑associated neurodegeneration.

Intrauterine growth restriction (IUGR) is a leading cause of perinatal morbidity and mortality. Oxidative stress is a key factor in the pathogenesis of IUGR. The transcription factor nuclear factor erythroid 2‑related factor 2 (Nrf2) is a key regulator of the cellular antioxidant response. MOTS‑c, a 16‑amino acid peptide derived from the mitochondria, regulates oxidative stress related pathways. However, the effects of MOTS‑c on IUGR remain unclear. The present study aimed to investigate the role of MOTS‑c in hypoxia‑induced placental restriction and IUGR and its underlying mechanisms. Wild‑type and Nrf2 knockout (KO) maternal mice were exposed to hypoxia from gestational days 11 to 17.5 to establish the IUGR model. Human umbilical vein endothelial cells (HUVECs) were used for in vitro assays. Maternal serum and placenta MOTS‑c concentration were measured using an enzyme‑linked immunosorbent assay. Hematoxylin and eosin staining, reverse transcription‑quantitative PCR, western blotting, immunohistochemistry and immunofluorescence techniques were employed to evaluate the effects of MOTS‑c treatment on IUGR. It was found that reduced placental content of MOTS‑c was positively correlated with low fetal weight in mice with hypoxia‑induced IUGR. The administration of MOTS‑c (5 mg/kg) significantly attenuated hypoxia‑induced IUGR by promoting placental angiogenesis and inhibiting oxidative stress‑mediated placental dysfunction. Furthermore, these protective effects exerted by MOTS‑c were dependent on Nrf2 activation, as administration of MOTS‑c had no protective role in Nrf2 KO mice or HUVECs pre‑treated with ML385, a Nrf2 inhibitor. Taken together, the present study demonstrated that MOTS‑c mitigated placental injury in hypoxia‑induced IUGR by activation of the Nrf2 signaling pathway, thus potentially identifying a novel therapeutic strategy for hypoxia‑induced IUGR.

Histone acetylation modification represents a common epigenetic regulatory mechanism, carrying out an indispensable role in cellular gene transcription and function. Histone deacetylases (HDACs) are responsible for regulating gene expression by controlling the deacetylation of histones and non‑histone proteins, and can serve as effective targets for participating in immune regulation. Short‑chain fatty acids (SCFAs) are important metabolites produced by the gut microbiota that modulate host immunity. SCFAs possess extensive inhibitory activities on class I and II HDACs, as well as acetylation‑modifying effects. Based on these, the present review initially introduces the microbial synthesis and intestinal absorption of SCFAs, as well as the classification and function of HDACs. Subsequently, the present review comprehensively summarizes the direct regulatory effects of SCFAs on immune cells through HDAC inhibition, encompassing innate immune cells (macrophages, dendritic cells, neutrophils, mast cells and natural killer cells) as well as T/B lymphocytes. Moreover, the present review further discusses the local intestinal and extra‑intestinal (primarily involving the liver, kidney, nerves and blood vessels) protective effects of SCFAs, which are mediated by their HDAC‑inhibiting activities. Finally, the present review summarizes the therapeutic potential of SCFAs as effective HDAC inhibitors in ameliorating intestinal and extra‑intestinal diseases and discusses the research prospects. The present review aims to elucidate the regulatory effects of SCFAs on host immunity through HDAC inhibition, highlighting their therapeutic potential for human diseases.

Studies have linked the dysregulation of N6‑methyladenosine (m6A) to sepsis‑induced acute kidney injury (SAKI), highlighting the persistent challenge of managing excessive proinflammatory cytokine production and subsequent organ dysfunction. The present study, by analyzing the GSE32707 and GSE69063 datasets, found that fat mass and obesity‑associated protein (FTO) was the sole m6A‑related gene markedly downregulated in the peripheral blood transcriptome of patients with sepsis. It further demonstrated that septic mice subjected to cecal ligation and puncture presented increased m⁶A modifications and reduced FTO expression in both renal tissues and peritoneal macrophages. The findings revealed that increased levels of FTO was associated with reduced mortality and kidney damage during sepsis and that the upregulation of FTO in lipopolysaccharide‑stimulated macrophages led to decreased production of proinflammatory cytokines. Mechanistically, through multiomic analysis of macrophages, the present study identified a novel mechanism involving matrix metalloproteinase 9 (MMP‑9) as a direct target of FTO, which positively affects its translation efficacy. Furthermore, both in vivo and in vitro data confirmed that reduced MMP‑9 levels exerted adverse effects on mitigating inflammatory responses and alleviating renal injury. Overall, the findings underscored the critical role of the FTO/m⁶A/MMP‑9 axis in the regulation of proinflammatory secretion and improved our understanding of the transcriptomic landscape during the progression of SAKI, suggesting that targeting the FTO/m⁶A/MMP‑9 axis may offer therapeutic potential for mitigating renal injury in septic patients.

Amino acid (AA) sensing plays an important role in maintaining cellular metabolic homeostasis as well as tumorigenesis and progression. Studies on classic AA sensing pathways such as rapamycin complex 1 (mTORC1) and general control nonderepressible 2 (GCN2) have revealed their central position in cancer metabolic reprogramming. AA sensing pathways are often hijacked in tumors to adapt to the nutrient‑deprived microenvironment, promoting cell proliferation, anti‑apoptosis and treatment tolerance. In addition, the regulation of AA sensing and transport plays a crucial role in maintaining the metabolic flexibility of tumor cells. By targeting the AA sensing mechanism, it is expected to disrupt the metabolic homeostasis of cancer cells, providing new strategies for precision therapy. The present review summarized the latest advances in the research on the role of the mTORC1 and GCN2 AA sensing pathways in tumor metabolism, emphasizing their potential and the challenges faced in cancer diagnosis and treatment. Additionally, it provided novel insights into the therapeutic targeting of AA sensing pathways and proposes future research directions aimed at overcoming current limitations in cancer metabolism therapy.

Temporomandibular joint (TMJ) synovitis is a chronic inflammatory condition prevalent in temporoman-dibular disorders, characterized by synovial inflammation and bone degradation. Quercetin, a natural flavonoid with diverse bioactive properties, is investigated for its potential in ameliorating TMJ synovitis by targeting the p38 MAPK pathway. Using network pharmacology and in vitro and in vivo models, the effects of quercetin on synoviocytes and inflammatory responses were evaluated. Results showed quercetin's significant inhibition of synoviocyte proliferation, promotion of apoptosis and reduction of inflammatory cytokines. Moreover, quercetin demonstrated stability in binding to critical targets like MAPK14 and led to downregulation of phosphorylated p38 MAPK and JNK. In vivo, quercetin improved synovial tissue architecture and mitigated bone destruction. Mechanistic studies confirmed the dependency of effects of quercetin on the p38 MAPK pathway, supported by functional experiments using pathway agonists and inhibitors. The present study underscored the potential of quercetin in treating TMJ synovitis by modulating inflammatory signaling, promoting cell apoptosis and preserving bone integrity, thereby offering novel insights into therapeutic strategies for TMJ‑related synovitis.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that most of the flow cytometric data shown in Fig. 5A on p. 1020 were strikingly similar to data which had been already been submitted for publication to several other journals that were written by different authors at different research institutes. Owing to the fact that the contentious data in the above article were found to be strikingly similar to data that had already been submitted, or accepted, for publication elsewhere, the Editor of International Journal of Molecular Medicine 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. [International Journal of Molecular Medicine 46: 1013‑1028, 2020; DOI: 10.3892/ijmm.2020.4649].

MicroRNA‑155 (miR‑155), a highly conserved non‑coding RNA, serves a pivotal role in the initiation and progression of cardiovascular and cerebrovascular diseases (CCVDs) through the modulation of target gene expression. miR‑155 contributes to the pathogenesis of conditions such as atherosclerosis, myocardial infarction, heart failure, hypertension and stroke, with mechanisms involving the regulation of endothelial function, inflammatory responses, oxidative stress, apoptosis and fibrosis. These findings suggest its potential as a biomarker. The present review provides a comprehensive overview of the biogenesis, regulation and biological functions of miR‑155, highlights its molecular mechanisms in CCVD progression, and examines current advances in therapeutic strategies targeting miR‑155, offering insights into the pathological mechanisms and precision treatment approaches for CCVDs.