International journal of molecular medicine最新文献

{"title":"Molecular mechanisms and clinicopathological characteristics of inhibin βA in thyroid cancer metastasis.","authors":"Wanjun Zhao, Weiyu Wang, Yifan Zhu, Zhenghua Lv, Wei Xu","doi":"10.3892/ijmm.2024.5423","DOIUrl":"https://doi.org/10.3892/ijmm.2024.5423","url":null,"abstract":"<p><p>The present study aimed to investigate the role and mechanism of inhibin βA (INHBA) in thyroid cancer (TC), and to determine its potential impact on the aggressive behavior of TC cells. The present study employed a comprehensive approach, using public databases, such as the Gene Expression Omnibus and The Cancer Genome Atlas, to identify and analyze the expression of INHBA in TC. Cell transfection, reverse transcription‑quantitative PCR, western blot analysis, immunohistochemistry and <i>in vivo</i> assays were conducted to investigate the functional effects of INHBA on TC. In addition, the present study explored the molecular mechanisms underlying the effects of INHBA, focusing on the potential impact on the RhoA signaling pathway and associated molecular cascades. Bioinformatics analysis revealed a significant association between INHBA expression and TC, and INHBA expression was markedly upregulated in TC tissues compared with in healthy control tissues. The results of functional studies demonstrated that INHBA overexpression increased the migration and invasion of TC cells, and the opposite result was observed following INHBA knockdown. Mechanistic investigations indicated that INHBA modulated the RhoA pathway, leading to alterations in the phosphorylation status of LIM kinase 1 (LIMK) and cofilin, key regulators of cytoskeletal dynamics and cell motility. Following the introduction of transfected TC cells into zebrafish and nude mouse models, the results of the present study demonstrated that INHBA knockdown attenuated the metastatic potential of TC cells. In conclusion, INHBA may serve a pivotal role in promoting the aggressive phenotype of TC cells through modulating the RhoA/LIMK/cofilin signaling axis. These findings highlight INHBA as a potential biomarker and therapeutic target for the management of aggressive TC.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286477","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":"Topical calcineurin and mammalian target of rapamycin inhibitors in inflammatory dermatoses: Current challenges and nanotechnology‑based prospects (Review).","authors":"Polytimi Sidiropoulou, Martha Katsarou, Maria Sifaki, Maria Papasavva, Nikolaos Drakoulis","doi":"10.3892/ijmm.2024.5409","DOIUrl":"10.3892/ijmm.2024.5409","url":null,"abstract":"<p><p>Topical therapy remains a critical component in the management of immune‑mediated inflammatory dermatoses such as psoriasis and atopic dermatitis. In this field, macrolactam immunomodulators, including calcineurin and mammalian target of rapamycin inhibitors, can offer steroid‑free therapeutic alternatives. Despite their potential for skin‑selective treatment compared with topical corticosteroids, the physicochemical properties of these compounds, such as high lipophilicity and large molecular size, do not meet the criteria for efficient penetration into the skin, especially with conventional topical vehicles. Thus, more sophisticated approaches are needed to address the pharmacokinetic limitations of traditional formulations. In this regard, interest has increasingly focused on nanoparticulate systems to optimize penetration kinetics and enhance the efficacy and safety of topical calcineurin and mTOR inhibitors in inflamed skin. Several types of nanovectors have been explored as topical carriers to deliver tacrolimus in both psoriatic and atopic skin, while preclinical data on nanocarrier‑based delivery of topical sirolimus in inflamed skin are also emerging. Given the promising preliminary outcomes and the complexities of drug delivery across inflamed skin, further research is required to translate these nanotherapeutics into clinical settings for inflammatory skin diseases. The present review outlined the dermatokinetic profiles of topical calcineurin and mTOR inhibitors, particularly tacrolimus, pimecrolimus and sirolimus, focusing on their penetration kinetics in psoriatic and atopic skin. It also summarizes the potential anti‑inflammatory benefits of topical sirolimus and explores novel preclinical studies investigating dermally applied nanovehicles to evaluate and optimize the skin delivery, efficacy and safety of these 'hard‑to‑formulate' macromolecules in the context of psoriasis and atopic dermatitis.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916639","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":"Current strategies for nonalcoholic fatty liver disease treatment (Review).","authors":"Jing Sun, Xiuli Jin, Yiling Li","doi":"10.3892/ijmm.2024.5412","DOIUrl":"10.3892/ijmm.2024.5412","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD), the most common chronic hepatic disease, has become a leading health problem worldwide. The present review summarized the methods and mechanisms to treat NAFLD, including the Mediterranean diet, physical activity and exercise, bariatric surgery and specific therapeutic agents, including statins, peroxisome proliferator‑activated receptor agonists, cenicriviroc and farnesoid X receptor agonists. Biologically active substances, such as peptides, alkaloids, polyphenolic compounds, silymarin, antibiotics, fatty acids, vitamins, probiotics, synbiotics and lamiaceae have also demonstrated actions that combat NAFLD. Considering their different mechanisms of action, combining some of them may prove an efficacious treatment for NAFLD. In this light, the present review describes recent progress and future prospects in treating NAFLD.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916674","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":"Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis.","authors":"Xiaoxin He, Kuanmin Tian, Xue Lin, Xiaolei Chen, Yajing Su, Zhidong Lu, Zhirong Chen, Liang Zhang, Peng Li, Long Ma, Gangning Feng, Xin Zhao, Zhibin Lan, Chen Zhang, Di Xue, Qunhua Jin","doi":"10.3892/ijmm.2024.5410","DOIUrl":"10.3892/ijmm.2024.5410","url":null,"abstract":"<p><p>Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone. The results suggest that Ras homolog family member A (RhoA) may be associated with the vascular permeability of subchondral bone and ferroptosis in OA. The results of analysis of clinical samples indicated a significant increase in expression of RhoA in the subchondral bone of OA. This were consistent with the proteomics findings. We found through western blotting, RT‑PCR, and immunofluorescence that RhoA significantly increased the permeability of endothelial cells (ECs) by inhibiting inter‑EC adhesion proteins (zona occludens‑1, connexin 43 and Vascular endothelial‑Cadherin) and actin filaments. Furthermore, RhoA induced ferroptosis core proteins (glutathione peroxidase 4,  solute carrier family 7 member 11 and acyl‑CoA synthase long‑chain family member 4, ACSL4) by influencing lipid peroxidation and mitochondrial function, leading to ferroptosis of ECs. This suggested an association between RhoA, ferroptosis and vascular permeability. Ferroptosis significantly increased permeability of ECs by inhibiting inter‑EC adhesion proteins. RhoA increased vascular permeability by inducing ferroptosis of ECs. <i>In vivo</i>, inhibition of RhoA and ferroptosis significantly mitigated progression of OA by alleviating cartilage degeneration and subchondral bone remodeling in mice with destabilization of the medial meniscus. In conclusion, the present findings indicated that RhoA enhanced vascular permeability in OA by inducing ferroptosis. This may serve as a novel strategy for the early prevention and treatment of OA.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916640","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 exosomal non‑coding RNAs in ovarian cancer (Review).","authors":"Xinchen Wang, Miao Yang, Jiamei Zhu, Yu Zhou, Gencui Li","doi":"10.3892/ijmm.2024.5411","DOIUrl":"10.3892/ijmm.2024.5411","url":null,"abstract":"<p><p>Ovarian cancer (OC) is a common gynecological disease with a high mortality rate worldwide due to its insidious nature and undetectability at an early stage. The standard treatment, combining platinum‑based chemotherapy with cytoreductive surgery, has suboptimal results. Therefore, early diagnosis of OC is crucial. All cell types secrete extracellular vesicles, particularly exosomes. Exosomes, which contain lipids, proteins, DNA and non‑coding RNAs (ncRNAs), are novel methods of intercellular communication that participate in tumor development and progression. ncRNAs are categorized by size into long ncRNAs (lncRNAs) and small ncRNAs (sncRNAs). sncRNAs further include transfer RNAs, small nucleolar RNAs, PIWI‑interacting RNAs and microRNAs (miRNAs). miRNAs inhibit protein translation and promote messenger RNA (mRNA) cleavage to suppress gene expression. By sponging downstream miRNAs, lncRNAs and circular RNAs can regulate target gene expression, thereby weakening the interactions between miRNAs and mRNAs. Exosomes and exosomal ncRNAs, commonly present in human biological fluids, are promising biomarkers for OC. The present article aimed to review the potential role of exosomal ncRNAs in the diagnosis and prognosis of OC by summarizing the characteristics, processes, roles and isolation methods of exosomes and exosomal ncRNAs.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916675","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":"Unveiling the multifaceted role of adropin in various diseases (Review).","authors":"Ling Chen, Jianrao Lu, Jing Hu, Xuezhong Gong","doi":"10.3892/ijmm.2024.5414","DOIUrl":"10.3892/ijmm.2024.5414","url":null,"abstract":"<p><p>Adropin is a secreted peptide encoded by the energy homeostasis‑associated gene, which also functions as a membrane‑bound protein facilitating intercellular communication. This peptide has been detected in various tissues and body fluids, including the brain, liver, kidney, heart, pancreas, small intestine, endothelial cells and colostrum. Notably, the amino acid sequences of adropin are identical in humans, mice and rats. Previous studies have demonstrated that adropin levels fluctuate under different physiological and pathological conditions. Adropin plays a role in regulating carbohydrate metabolism, lipid metabolism and intercellular molecular signaling pathways, implicating its involvement in the progression of numerous diseases, such as acute myocardial infarction, lung injury, non‑alcoholic fatty liver disease/non‑alcoholic steatohepatitis, kidney disease, polycystic ovary syndrome, obesity, and diabetes, atherosclerosis, systemic sclerosis and cancer. Despite its significance, the precise role and mechanism of this protein remain inadequately understood and studied. To elucidate the function of adropin and its clinical research status, a systematic review of recent studies on adropin across various diseases was conducted. Additionally, several challenges and limitations associated with adropin research in both animal and clinical contexts were identified, aiming to offer valuable insights for future investigation.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999851","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] Ginsenoside Rg1 inhibits inflammatory responses via modulation of the nuclear factor‑κB pathway and inhibition of inflammasome activation in alcoholic hepatitis.","authors":"Jiajun Li, Cheng Yang, Shu Zhang, Shu Liu, Luole Zhao, Huan Luo, Yatang Chen, Wenxiang Huang","doi":"10.3892/ijmm.2024.5407","DOIUrl":"10.3892/ijmm.2024.5407","url":null,"abstract":"<p><p>Following the publication of the above article, the authors drew to the attention of the Editorial Office that, after having reviewed all the figures and the data of their drawing software, they discovered that the pictures in the 'Control' and 'DEX' groups of Fig. 4D on p. 904 had been incorrectly imported into Fig. 6 on p. 905 when assembling this figure, effectively replacing the original and correctly placed images in Fig. 6D and E. The original (and correct) version of Fig. 6 is shown on the next page. All the authors agree with the publication of this Corrigendum, and express their gratitude to the Editor of <i>International Journal of Molecular Medicine</i> for allowing them the opportunity to publish this; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 41: 899‑907, 2018; DOI: 10.3892/ijmm.2017.3297].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874767","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":"Exploring the association between melatonin and nicotine dependence (Review).","authors":"Vasiliki Epameinondas Georgakopoulou, Pagona Sklapani, Nikolaos Trakas, Russel J Reiter, Demetrios A Spandidos","doi":"10.3892/ijmm.2024.5406","DOIUrl":"10.3892/ijmm.2024.5406","url":null,"abstract":"<p><p>Due to the addictive qualities of tobacco products and the compulsive craving and dependence associated with their use, nicotine dependence continues to be a serious public health concern on a global scale. Despite awareness of the associated health risks, nicotine addiction contributes to numerous acute and chronic medical conditions, including cardiovascular disease, respiratory disorders and cancer. The nocturnal secretion of pineal melatonin, known as the 'hormone of darkness', influences circadian rhythms and is implicated in addiction‑related behaviors. Melatonin receptors are found throughout the brain, influencing dopaminergic neurotransmission and potentially attenuating nicotine‑seeking behavior. Additionally, the antioxidant properties of melatonin may mitigate oxidative stress from chronic nicotine exposure, reducing cellular damage and lowering the risk of nicotine‑related health issues. In addition to its effects on circadian rhythmicity, melatonin acting via specific neural receptors influences sleep and mood, and provides neuroprotection. Disruptions in melatonin signaling may contribute to sleep disturbances and mood disorders, highlighting the potential therapeutic role of melatonin in addiction and psychiatric conditions. Melatonin may influence neurotransmitter systems involved in addiction, such as the dopaminergic, glutamatergic, serotonergic and endogenous opioid systems. Preclinical studies suggest the potential of melatonin in modulating reward processing, attenuating drug‑induced hyperactivity and reducing opioid withdrawal symptoms. Chronotherapeutic approaches targeting circadian rhythms and melatonin signaling show promise in smoking cessation interventions. Melatonin supplementation during periods of heightened nicotine cravings may alleviate withdrawal symptoms and reduce the reinforcing effects of nicotine. Further research is required however, to examine the molecular mechanisms underlying the melatonin‑nicotine association and the optimization of therapeutic interventions. Challenges include variability in individual responses to melatonin, optimal dosing regimens and identifying biomarkers of treatment response. Understanding these complexities could lead to personalized treatment strategies and improve smoking cessation outcomes.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874768","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":"TMEM16 proteins: Ca²⁺‑activated chloride channels and phospholipid scramblases as potential drug targets (Review).","authors":"Zeqi Huang, Zoya Iqbal, Zhe Zhao, Xiaoqiang Chen, Ayesha Mahmmod, Jianquan Liu, Wencui Li, Zhiqin Deng","doi":"10.3892/ijmm.2024.5405","DOIUrl":"10.3892/ijmm.2024.5405","url":null,"abstract":"<p><p>TMEM16 proteins, which function as Ca²⁺‑activated Cl^‑ channels are involved in regulating a wide variety of cellular pathways and functions. The modulators of Cl^‑ channels can be used for the molecule‑based treatment of respiratory diseases, cystic fibrosis, tumors, cancer, osteoporosis and coronavirus disease 2019. The TMEM16 proteins link Ca²⁺ signaling, cellular electrical activity and lipid transport. Thus, deciphering these complex regulatory mechanisms may enable a more comprehensive understanding of the physiological functions of the TMEM16 proteins and assist in ascertaining the applicability of these proteins as potential pharmacological targets for the treatment of a range of diseases. The present review examined the structures, functions and characteristics of the different types of TMEM16 proteins, their association with the pathogenesis of various diseases and the applicability of TMEM16 modulator‑based treatment methods.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874770","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":"[Retracted] Puerarin improves graft bone defect through microRNA‑155‑3p‑mediated p53/TNF‑α/STAT1 signaling pathway.","authors":"Yang Zhou, Hongyu Lian, Kexin Liu, Deli Wang, Xuelian Xiu, Zhang Sun","doi":"10.3892/ijmm.2024.5404","DOIUrl":"10.3892/ijmm.2024.5404","url":null,"abstract":"<p><p>Following the publication of the above paper, it has been drawn to the Editor's attention by a concerned reader that the immunohistochemical assay data shown in Fig. 4B on p. 245 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes that had already been published in the journal <i>International Journal of Biological Sciences</i> prior to the submission of this paper to <i>International Journal of Molecular Medicine</i>. In view of the fact that the contentious data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 46: 239-251, 2020; DOI: 10.3892/ijmm.2020.4595].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758519","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}