International journal of molecular medicine最新文献

{"title":"MTHFD2 promotes esophageal squamous cell carcinoma progression via m6A modification‑mediated upregulation and modulation of the PEBP1‑RAF1 interaction.","authors":"Huijun Zhou, Han Gong, Xiaohui Zeng, Chong Zeng, Dian Liu, Jie Liu, Yingying Zhang","doi":"10.3892/ijmm.2025.5509","DOIUrl":"10.3892/ijmm.2025.5509","url":null,"abstract":"<p><p>One‑carbon metabolism plays an important role in cancer progression. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme in one‑carbon metabolism, is dysregulated in several cancer types. However, the precise role and mechanisms of MTHFD2 in esophageal squamous cell carcinoma (ESCC) remain unclear. The present study unravels the multifaceted mechanisms by which MTHFD2 contributes to ESCC pathogenesis. Bioinformatics analyses revealed significant upregulation of MTHFD2 in ESCC tumor tissues, which was associated with advanced disease stage and poor patient prognosis. Validating these findings in clinical samples, MTHFD2 overexpression was confirmed through immunohistochemistry, Reverse transcription‑quantitative PCR and western blotting. Knockdown of MTHFD2 inhibited ESCC cell viability, colony formation, invasion, and tumor growth in vivo, indicating its oncogenic potential. Mechanistically, the present study elucidated a novel regulatory axis involving N6‑methyladenosine modification and MTHFD2 mRNA stability. Specifically, methyltransferase‑like 3 (METTL3) and insulin‑like growth factor 2 mRNA binding protein 2 (IGF2BP2) were identified as key mediators of m6A‑dependent stabilization of MTHFD2 mRNA, contributing to its elevated expression in ESCC. Furthermore, MTHFD2 was found to activate PI3K/AKT and ERK signaling pathways by modulating interaction between phosphatidylethanolamine‑binding protein 1 (PEBP1) and raf‑1 proto‑oncogene (RAF1). This modulation was achieved through direct binding of MTHFD2 to PEBP1, disrupting the inhibitory effect of PEBP1 on RAF1 and promoting downstream pathway activation. The oncogenic functions of MTHFD2 were attenuated upon PEBP1 knockdown, underscoring the role of the MTHFD2‑PEBP1 axis in ESCC progression. In summary, the present study uncovers a novel regulatory mechanism involving m6A modification and the MTHFD2‑PEBP1 axis, unveiling potential therapeutic avenues for targeting MTHFD2 in ESCC.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound C exerts a therapeutic effect on Graves' orbitopathy via AMPK‑independent pathways.","authors":"Hyun Young Park, Soo Hyun Choi, Hyeon Seo Lee, Jaesang Ko, Jin Sook Yoon","doi":"10.3892/ijmm.2025.5524","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5524","url":null,"abstract":"<p><p>Compound C is an adenosine monophosphate‑activated protein kinase (AMPK) inhibitor, which is also recognized as a broad‑spectrum kinase inhibitor with anti‑proliferative effects. The present study investigated the therapeutic effects of a high concentration of compound C on Graves' orbitopathy (GO) pathogenesis beyond the AMPK‑dependent pathway using human orbital fibroblasts. Orbital connective tissue was obtained from patients with GO and healthy controls, and primary orbital fibroblasts were cultured. The cells were then pretreated with a non‑cytotoxic concentration of compound C, and stimulated with either IL‑1β or TGF‑β. Pro‑inflammatory cytokine expression, profibrotic protein production and adipogenesis were evaluated using western blotting and Oil Red O staining. Adipocyte differentiation following knockdown of the hippocampal signaling pathway was also analyzed. Hyaluronan secretion was assessed using ELISA. Notably, treatment with a non‑cytotoxic concentration of compound C (10 µM) significantly suppressed AMPK and yes‑associated protein (YAP) phosphorylation in orbital fibroblasts. In addition, compound C suppressed IL‑1β‑induced pro‑inflammatory cytokine production and TGF‑β‑induced profibrotic protein production, as well as the phosphorylation of Akt, SMAD 1/2/3, and hyaluronan secretion. Similar to compound C treatment, silencing YAP and transcriptional co‑activator with PDZ‑binding motif, significantly attenuated adipogenesis as determined by Oil Red O quantification and the production of adipogenic markers. It may be hypothesized that a high concentration of compound C suppresses inflammation, fibrosis and adipogenesis in orbital fibroblasts through YAP inactivation, since YAP knockdown effectively reduced adipogenesis in GO orbital fibroblasts. Taken together, these findings suggested that compound C may exert its therapeutic effects through an AMPK‑independent mechanism, inhibiting inflammation, adipogenesis and fibrosis in orbital fibroblasts.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] MicroRNA‑132 induces temozolomide resistance and promotes the formation of cancer stem cell phenotypes by targeting tumor suppressor candidate 3 in glioblastoma.","authors":"Zhen-Xiu Cheng, Wen-Bo Yin, Zhong-Yu Wang","doi":"10.3892/ijmm.2025.5517","DOIUrl":"10.3892/ijmm.2025.5517","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the clonogenic agar assay data shown in Fig. 5C on p. 1312 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes, which had already been published in the journal <i>Oncotarget</i> prior to the submission of this paper to International Journal of Molecular Medicine. In view of the fact that the abovementioned data had already apparently been published previously, the Editor of <i>International Journal of Molecular Medicine</i> 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 40: 1307‑1314, 2017; DOI: 10.3892/ijmm.2017.3124].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seizures in brain tumors: pathogenesis, risk factors and management (Review).","authors":"Cyrille D Dantio, Deborah Oluwatosin Fasoranti, Chubei Teng, Xuejun Li","doi":"10.3892/ijmm.2025.5523","DOIUrl":"10.3892/ijmm.2025.5523","url":null,"abstract":"<p><p>Seizures in the context of brain tumors are a relatively common symptom, with higher occurrence rates observed in glioneuronal tumors and gliomas. It is a serious burden that can have a significant impact on the quality of life (QoL) of patients and influence the disease's prognosis. Brain tumor‑related epilepsy (BTRE) is a challenging entity because the pathophysiological mechanisms are not fully understood yet. Nonetheless, neuroinflammation is considered to play a pivotal role. Next to neuroinflammation, findings on the pathogenesis of BTRE have established that certain genetic mutations are involved, of which the most known would be IDH mutations in gliomas. Others discussed more thoroughly in the present review include genes such as PTEN, TP53, IGSF3, and these findings all provide fresh and fascinating insights into the pathogenesis of BTRE. Treatment for BTRE presents unique challenges, mainly related to burdens of polytherapy, debated necessity of anti‑epileptic prophylaxis, and overall impact on the QoL. In fact, there are no established anti‑seizure medications (ASMs) of choice for BTRE, nor is there any protocol to guide the use of these medications at every step of disease progression. Treatment strategies aimed at the tumor, that is surgical procedures, radio‑ and chemotherapy appear to influence seizure control. Conversely, some ASMs have also shown antitumor properties. The present review summarizes and retrospectively analyzes the literature on the pathogenesis and management of BTRE to provide an updated comprehensive understanding. Furthermore, the challenges and opportunities for developing future therapies aimed at BTRE are discussed.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitors of the ubiquitin‑proteasome system rescue cellular levels and ion transport function of pathogenic pendrin (SLC26A4) protein variants.","authors":"Emanuele Bernardinelli, Rapolas Jamontas, Arnoldas Matulevičius, Florian Huber, Houssein Nasser, Sophie Klaus, Haixia Zhu, Jiangang Gao, Silvia Dossena","doi":"10.3892/ijmm.2025.5510","DOIUrl":"10.3892/ijmm.2025.5510","url":null,"abstract":"<p><p>Pendrin (SLC26A4) is an anion exchanger abundantly expressed in the inner ear, kidney and thyroid, and its malfunction resulting from genetic mutation leads to Pendred syndrome and non‑syndromic deafness DFNB4. Pathogenic variants of the pendrin protein are less expressed than the wild‑type, but the mechanism underlying this phenomenon is unknown. In the present study, the hypothesis that reduced protein expression stems from increased protein degradation was explored. To verify this hypothesis, the protein levels and anion transport function of several pathogenic pendrin variants were measured following exposure to inhibitors of the ubiquitin‑proteasome system (UPS) and the lysosomal/autophagosomal pathways. Protein levels were measured by western blotting and quantitative imaging; ion transport was measured with a fluorometric method. Post‑translational modification of pendrin was investigated by immunoprecipitation and mass spectrometry. The results showed that the protein abundance and half‑life of pathogenic pendrin variants were significantly reduced compared with the wild‑type in cell‑based assays and in a mouse model of Pendred syndrome/DFNB4, pointing to accelerated protein degradation rather than defective protein production. Wild‑type pendrin and its variants are abundantly but differentially ubiquitinated, consistent with their different protein stability. While ubiquitination at the C‑terminus controls the stability of wild‑type pendrin, preferential ubiquitination of lysine 77 occurred in the pathogenic pendrin variant p.R409H. Inhibition of the UPS with investigational (MG132) or clinical (bortezomib, delanzomib, or carfilzomib) proteasome inhibitors rescued the expression, plasma membrane targeting, and ion transport function of pathogenic pendrin variants, while inhibition of the lysosomal/autophagosomal pathway was ineffective. Among the compounds tested, carfilzomib rescued the ion transport of pendrin p.R409H to wild‑type levels. These findings suggest that targeting specific molecular players within the UPS can rescue the expression and activity of pathogenic variants of the pendrin protein, which represents a novel therapeutic concept for Pendred syndrome/DFNB4.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulating FGGY carbohydrate kinase domain containing promotes cell senescence by activating the p53/p21 signaling pathway in colorectal cancer.","authors":"Liya Liu, Meizhu Wu, Youqin Chen, Ying Cheng, Sijia Liu, Xinran Zhang, Qiurong Xie, Liujing Cao, Lihui Wei, Yi Fang, Anjum Jafri, Thomas J Sferra, Aling Shen, Li Li","doi":"10.3892/ijmm.2025.5522","DOIUrl":"10.3892/ijmm.2025.5522","url":null,"abstract":"<p><p>Carbohydrate kinases serve an oncogenic role in several types of cancer; however, the function of FGGY carbohydrate kinase domain containing (FGGY) in colorectal cancer (CRC) remains unknown. The present study investigated the function and possible molecular mechanisms of FGGY in CRC. The results showed that elevated levels of FGGY mRNA and protein were observed in CRC tissues, and a higher expression of FGGY was associated with advanced N stage and reduced overall survival time in patients with CRC. Silencing FGGY inhibited the viability of CRC cells by inducing cell cycle arrest and promoting apoptosis <i>in vitro</i>, thereby attenuating tumor growth in a xenograft mouse model. FGGY knockdown also enriched the senescence‑associated heterochromatin foci (SAHF) pathway and p53 pathway, as further confirmed by enhancing senescence‑associated β‑galactosidase (SA‑β‑gal) activity, with increased levels of SAHF‑associated proteins HP1γ and trimethylation of H3K9 (H3k9me3) in CRC cells, as well as upregulation of p53 and its downstream protein p21. Furthermore, p53 knockout rescued FGGY knockdown‑mediated reductions in cell viability, SA‑β‑gal activity, and the levels of HP1γ and H3k9me3 in CRC cells. These findings indicated that FGGY could act as a newly identified potential oncogene in CRC, partially through regulating the p53/p21 signaling pathway and altering cell senescence.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Corrigendum] Use of methylation profiling to identify significant differentially methylated genes in bone marrow mesenchymal stromal cells from acute myeloid leukemia.","authors":"Jing Huang, Zhi Liu, Yufan Sun, Qi Zhong, Li Xu, Ruimin Ou, Cheng Li, Rui Chen, Mengdong Yao, Qing Zhang, Shuang Liu","doi":"10.3892/ijmm.2025.5520","DOIUrl":"10.3892/ijmm.2025.5520","url":null,"abstract":"<p><p>Following the publication of the above article, an interested reader drew to the authors' and the Editor's attention that, given the subject matter of the article, in a few places in the text throughout the paper, 'MIR159' was probably intended to have been written as 'MIR596', and 'miR‑159' was probably meant to have been written as 'miR‑596'. The authors have responded to confirm that the interested reader was correct in their assessment; this paper discusses the role of miR‑596 in the context of acute myeloid leukemia (AML) and its potential as a biomarker, and this error appears to have occurred during the final stages of manuscript preparation. Therefore, the following corrections to the text of this article should be noted:  a) In the final sentence of the Abstract on p. 679, 'miR‑596' should have been written, rather than 'miR‑159'. The corrected sentence should read as follows: 'Furthermore, the aberrantly hypermethylated <b>miR‑596</b>‑encoding gene <i><b>MIR596</b></i> may be a potential biomarker of AML.' b) In the Discussion, all instances where 'miR‑159' and 'MIR159' were mentioned should be corrected to 'miR‑596' and 'MIR596', respectively. The sentences concerned should have read as follows (p. 685, right‑hand column, line 9): 'Thus, it was suggested that the hypermethylation of <b>miR‑596</b> may be associated with its transcriptional regulation. It was also inferred that <b>miR‑596</b> methylation in BM‑MSCs may be a biomarker or prognostic factor for patients with AML. However, the significance of the methylation of miR‑596 demands further investigation.\" In addition, the sentence starting on p. 685, right‑hand column, second paragraph, line 5, should have read as follows: 'Furthermore, the aberrant hypermethylated <b>miR‑596</b>‑encoding gene <i><b>MIR596</b></i> may be a potential biomarker of AML.' All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Molecular Medicine  41: 679‑686, 2018; DOI: 10.3892/ijmm.2017.3271].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of GLP‑1 receptor agonists in sepsis and their therapeutic potential in sepsis‑induced muscle atrophy (Review).","authors":"Xuan Zhao, Yukun Liu, Dongfang Wang, Tonghan Li, Zhikai Xu, Zhanfei Li, Xiangjun Bai, Yuchang Wang","doi":"10.3892/ijmm.2025.5515","DOIUrl":"10.3892/ijmm.2025.5515","url":null,"abstract":"<p><p>Sepsis‑induced myopathy (SIM) is a common complication in intensive care units, which is often associated with adverse outcomes, primarily manifested as skeletal muscle weakness and atrophy. Currently, the management of SIM focuses on prevention strategies, as effective therapeutic options remain elusive. Glucagon‑like peptide‑1 (GLP‑1) receptor agonists (GLP‑1RAs) have garnered attention as hypoglycemic and weight‑loss agents, with an increasing body of research focusing on the extrapancreatic effects of GLP‑1. In preclinical settings, GLP‑1RAs exert protective effects against sepsis‑related multiple organ dysfunction through anti‑inflammatory and antioxidant mechanisms. Based on the existing research, we hypothesized that GLP‑1RAs may serve potential protective roles in the repair and regeneration of skeletal muscle affected by sepsis. The present review aimed to explore the relationship between GLP‑1RAs and sepsis, as well as their impact on muscle atrophy‑related myopathy. Furthermore, the potential mechanisms and therapeutic benefits of GLP‑1RAs are discussed in the context of muscle atrophy induced by sepsis.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of lysine lactylation in neoplastic and inflammatory pulmonary diseases (Review).","authors":"Shanshan Wang, Hongyan Zheng, Jianping Zhao, Jungang Xie","doi":"10.3892/ijmm.2025.5512","DOIUrl":"10.3892/ijmm.2025.5512","url":null,"abstract":"<p><p>Protein lysine lactylation is a ubiquitous and post‑translational modification of lysine residues that involves the addition of a lactyl group on both histone and non‑histone proteins. This process plays a pivotal role in human health and disease and was first discovered in 2019. This epigenetic modification regulates gene transcription from chromatin or directly influences non‑histone proteins by modulating protein‑DNA/protein interactions, activity and stability. The dual functions of lactylation in both histone and non‑histone proteins establish it as a crucial mechanism involved in various cellular processes, such as cell proliferation, differentiation, immune and inflammatory responses and metabolism. Specific enzymes, referred to as 'writers' and 'erasers', catalyze the addition or removal of lactyl groups at designated lysine sites, thereby dynamically modulating lactylation through alterations in their enzymatic activities. The respiratory system has a remarkably intricate metabolic profile. Numerous pulmonary diseases feature an atypical transition towards glycolytic metabolism, which is linked to an overproduction of lactate, a possible substrate for lactylation. However, there has yet to be a comprehensive review elucidating the full impact of lactylation on the onset, progression and potential treatment of neoplastic and inflammatory pulmonary diseases. In the present review, an extensive overview of the discovery of lactylation and advancements in research on the existing lactylation sites were discussed. Furthermore, the review particularly investigated the potential roles and mechanisms of histone and non‑histone lactylation in various neoplastic and inflammatory pulmonary diseases, including non‑small cell lung cancers, malignant pleural effusion, pulmonary fibrosis, acute lung injury and asthma, to excavate the new therapeutic effects of post‑translational modification on various pulmonary diseases.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance of STAT3 signaling in preeclampsia (Review).","authors":"Daniela Marzioni, Federica Piani, Nicoletta Di Simone, Stefano Raffaele Giannubilo, Andrea Ciavattini, Giovanni Tossetta","doi":"10.3892/ijmm.2025.5499","DOIUrl":"10.3892/ijmm.2025.5499","url":null,"abstract":"<p><p>Placentation is a key process that is tightly regulated that ensures the normal placenta and fetal development. Preeclampsia (PE) is a hypertensive pregnancy‑associated disorder characterized by increased oxidative stress and inflammation. STAT3 signaling plays a key role in modulating important processes such as cell proliferation, differentiation, invasion and apoptosis. The present review aimed to analyse the role of STAT3 signaling in PE pregnancies, discuss the main natural and synthetic compounds involved in modulation of this signaling both <i>in vivo</i> and <i>in vitro</i> and summarize the main cellular modulators of this signaling to identify possible therapeutic targets and treatments to improve the outcome of PE pregnancies.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}