International journal of molecular medicine最新文献

{"title":"Inhibition of HDAC6 alleviates cancer‑induced bone pain by reducing the activation of NLRP3 inflammasome.","authors":"Yin-Di Hu, Zhao-Di Wang, Yuan-Fen Yue, Dai Li, Shu-Qing Zhen, Jie-Qiong Ding, Wei Meng, Hai-Li Zhu, Min Xie, Ling Liu","doi":"10.3892/ijmm.2023.5328","DOIUrl":"10.3892/ijmm.2023.5328","url":null,"abstract":"<p><p>Cancer‑induced bone pain (CIBP) is characterized as moderate to severe pain that negatively affects the daily functional status and quality of life of patients. When cancer cells metastasize and grow in bone marrow, this activates neuroinflammation in the spinal cord, which plays a vital role in the generation and persistence of chronic pain. In the present study, a model of CIBP was constructed by inoculating of MRMT‑1 rat breast carcinoma cells into the medullary cavity of the tibia in male Sprague‑Dawley rats. Following two weeks of surgery, CIBP rats exhibited damaged bone structure, increased pain sensitivity and impaired motor coordination. Neuroinflammation was activated in the spinal cords of CIBP rats, presenting with extensive leukocyte filtration, upregulated cytokine levels and activated astrocytes. Histone deacetylase 6 (HDAC6) works as a therapeutic target for chronic pain. The intrathecal injection of the HDAC6 inhibitor tubastatin A (TSA) in the lumbar spinal cord resulted in decreased spinal inflammatory cytokine production, suppressed spinal astrocytes activation and reduced NOD‑like receptor pyrin domain containing 3 (NLRP3) inflammasome activity. Consequently, this effect alleviated spontaneous pain and mechanical hyperalgesia and recovered motor coordination in CIBP rats. It was demonstrated by immunoprecipitation assay that TSA treatment reduced the interaction between HDAC6 and NLRP3. Cell research on C6 rat glioma cells served to verify that TSA treatment reduced HDAC6 and NLRP3 expression. In summary, the findings of present study indicated that TSA treatment alleviated cancer‑induced bone pain through the inhibition of HDAC6/NLRP3 inflammasome signaling in the spinal cord.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299057","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":"mROS‑calcium feedback loop promotes lethal ventricular arrhythmias and sudden cardiac death in early myocardial ischemia.","authors":"Danya Zhou, Ye Zhang, Mengting Zhu, Xiaojun Zhang, Xiaojuan Zhang, Junyao Lv, Wanting Tang, Qi Weng, Yang Lin, Lejun Tong, Zhiwei Zhong, Yanmei Zhang, Mengxuan Zhang, Minchao Lai, Dian Wang","doi":"10.3892/ijmm.2023.5329","DOIUrl":"10.3892/ijmm.2023.5329","url":null,"abstract":"<p><p>Lethal ventricular arrhythmia‑sudden cardiac death (LVA‑SCD) occurs frequently during the early stage of myocardial ischemia (MI). However, the mechanism underlying higher LVA‑SCD incidence is still poorly understood. The present study aimed to explore the role of mitochondrial reactive oxygen species (mROS) and Ca²⁺ crosstalk in promoting LVA‑SCD in early MI. RyR2 S2814A mice and their wild‑type littermates were used. MitoTEMPO was applied to scavenge mitochondrial ROS (mROS). Mice were subjected to severe MI and the occurrence of LVA‑SCD was evaluated. Levels of mitochondrial ROS and calcium (mitoCa²⁺), cytosolic ROS (cytoROS), and calcium (cytoCa²⁺), RyR2 Ser‑2814 phosphorylation, CaMKII Met‑282 oxidation, mitochondrial membrane potential (MMP), and glutathione/oxidized glutathione (GSH/GSSG) ratio in the myocardia were detected. Dynamic changes in mROS after hypoxia were investigated using H9c2 cells. Moreover, the myocardial phosphoproteome was analyzed to explore the related mechanisms facilitating mROS‑Ca²⁺ crosstalk and LVA‑SCD. There was a high incidence (~33.9%) of LVA‑SCD in early MI. Mice who underwent SCD displayed notably elevated levels of myocardial ROS and mROS, and the latter was validated in H9c2 cells. These mice also demonstrated overloads of cytoplasmic and mitochondrial Ca²⁺, decreased MMP and reduced GSH/GSSG ratio, upregulated RyR2‑S2814 phosphorylation and CaMKII‑M282 oxidation and transient hyperphosphorylation of mitochondrial proteomes in the myocardium. mROS‑specific scavenging by a mitochondria‑targeted antioxidant agent (MitoTEMPO) corrected these SCD‑induced alterations. S2814A mice with a genetically inactivated CaMKII phosphorylation site in RyR2 exhibited decreased overloads in cytoplasmic and mitochondrial Ca²⁺ and demonstrated similar effects as MitoTEMPO to correct SCD‑induced changes and prevent SCD post‑MI. The data confirmed crosstalk between mROS and Ca2+ in promoting LVA‑SCD. Therefore, we provided evidence that there is a higher incidence of LVA‑SCD in early MI, which may be attributed to a positive feedback loop between mROS and Ca²⁺ imbalance.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10712693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299058","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] Downregulation of long non‑coding RNA GACAT1 suppresses proliferation and induces apoptosis of NSCLC cells by sponging microRNA‑422a.","authors":"Youqing Zhong, Hui Lin, Qi Li, Chang Liu, Lei Zhong","doi":"10.3892/ijmm.2023.5325","DOIUrl":"10.3892/ijmm.2023.5325","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the flow cytometric data shown in Fig. 2E on p. 662 were strikingly similar to data appearing in different form in a pair of other research articles written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication elsewhere prior to its submission to <i>International Journal of Molecular Medicine</i>, 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 never received a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 659‑667, 2021; DOI: 10.3892/ijmm.2020.4826].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481339","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":"Roles of vitamin K‑dependent protein in biomineralization (Review).","authors":"Meng Zhang, Qingqi Zhang, Pengfei Du, Xin Chen, Yumei Zhang","doi":"10.3892/ijmm.2023.5330","DOIUrl":"10.3892/ijmm.2023.5330","url":null,"abstract":"<p><p>Vitamin K (VK), a fat‑soluble vitamin, is well known as an anticoagulant in the clinic. It is essential for the post‑translational activation of VK‑dependent proteins (VKDPs) because hydroquinone VK is a cofactor of glutamine carboxylase. At present, 17 VKDPs are known, which are mainly involved in coagulation and calcification. When Glu residues are carboxylated to Gla residues, these proteins gain a higher calcium‑binding ability, which explains why VK has an important role in blood coagulation and biomineralization. However, the current view on the role of VK and several VKDPs in biomineralization remains inconsistent. For instance, conflicting results have been reported regarding the effect of <i>osteocalcin</i> gene knockout on the bone of mice; matrix Gla protein (MGP) promotes osteoblasts mineralization but inhibits vascular smooth muscle cell mineralization. The present review aimed to summarize the existing evidence that several VKDPs, including osteocalcin, MGP, Gla‑rich protein and growth arrest specific 6 are closely related to calcification, including bone health, vascular calcification and lithiasis. The current review discussed these controversies and provided suggestions for future studies on VKDPs, i.e. taking into account dietary habits, geographical environments and genetic backgrounds.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10712699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299059","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":"Combination of the cuproptosis inducer disulfiram and anti‑PD‑L1 abolishes NSCLC resistance by ATP7B to regulate the HIF‑1 signaling pathway","authors":"Pengfei Li, Qi Sun, Shuping Bai, Haitao Wang, Ling Zhao","doi":"10.3892/ijmm.2023.5343","DOIUrl":"https://doi.org/10.3892/ijmm.2023.5343","url":null,"abstract":"","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139152625","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":"Comparison of HepaRG and HepG2 cell lines to model mitochondrial respiratory adaptations in non‑alcoholic fatty liver disease","authors":"Tumisang E. Maseko, M. Elkalaf, Eva Peterová, H. Lotková, P. Staňková, Jan Melek, Jan Dušek, Petra Žádníková, Dana Čížková, A. Bezrouk, Petr Pávek, Zuzana Červinková, O. Kučera","doi":"10.3892/ijmm.2023.5342","DOIUrl":"https://doi.org/10.3892/ijmm.2023.5342","url":null,"abstract":"","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138945585","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] Rotenone restrains colon cancer cell viability, motility and epithelial‑mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway.","authors":"Wenbo Xiao, Yongwei Liu, Maolin Dai, Yu Li, Renqun Peng, Shuangjiang Yu, Hao Liu","doi":"10.3892/ijmm.2023.5340","DOIUrl":"https://doi.org/10.3892/ijmm.2023.5340","url":null,"abstract":"Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the immunofluorescence staining data shown in Fig. 3C, and the migration and invasion assay data shown in Figs. 4C and 4D were strikingly similar to data appearing in different form in other research articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time, one of which has been retracted. In addition, the western blotting data shown for the E‑cadherin and AKT protein bands in Fig. 5 were strikingly similar, albeit the bands had been flipped vertically. Owing to the fact that contentious data in the above article had already been submitted for publication elsewhere prior to its submission to <i>International Journal of Molecular Medicine</i>, 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. [International Journal of Molecular Medicine 44: 700‑708, 2020; DOI: 10.3892/ijmm.2020.4637].","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138686529","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":"An LGR4 agonist activates the GSK‑3β pathway to inhibit RANK‑RANKL signaling during osteoclastogenesis in bone marrow‑derived macrophages.","authors":"Yuria Jang, Hyeonjoon Lee, Yongjin Cho, Eunseo Choi, Suenghwan Jo, Hong Moon Sohn, Beom Chang Kim, Young Jong Ko, Wonbong Lim","doi":"10.3892/ijmm.2023.5334","DOIUrl":"https://doi.org/10.3892/ijmm.2023.5334","url":null,"abstract":"The binding between receptor‑activated nuclear factor‑κB (RANK) and the RANK ligand (RANKL) during osteoclast development is an important target for drugs that treat osteoporosis. The leucine‑rich repeat‑containing G‑protein‑coupled receptor 4 (LGR4) acts as a negative regulator of RANK‑RANKL that suppresses canonical RANK signaling during osteoclast differentiation. Therefore, LGR4 agonists may be useful in inhibiting osteoclastogenesis and effectively treating osteoporosis. In the present study, bone marrow‑derived macrophages and a mouse model of RANKL‑induced bone loss were used to investigate the effect of mutant RANKL (MT RANKL), which was previously developed based on the crystal structure of the RANKL complex. In the present study, the binding affinity of wild‑type (WT) RANKL and MT RANKL to RANK and LGR4 was determined using microscale thermophoresis analysis, and the effect of the ligands on the AKT‑glycogen synthase kinase‑3β (GSK‑3β)‑nuclear factor of activated T cells, cytoplasmic, calcineurin‑dependent 1 (NFATc1) signaling cascade was investigated using western blotting and confocal microscopy. In addition, the expression of LGR4 and the colocalization of LGR4 with MT RANKL were analyzed in a mouse model of RANKL‑induced bone loss. The results showed that in osteoclast precursor cells, MT RANKL bound with high affinity to LGR4 and increased GSK‑3β phosphorylation independently of AKT, resulting in the inhibition of NFATc1 nuclear translocation. In the mouse model, MT RANKL colocalized with LGR4 and inhibited bone resorption. These results indicated that MT RANKL may inhibit RANKL‑induced osteoclastogenesis through an LGR4‑dependent pathway and this could be exploited to develop new therapies for osteoporosis.","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138560349","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":"Nrf2 protects against cartilage endplate degeneration through inhibiting NCOA4‑mediated ferritinophagy.","authors":"Zhenkai Ma, Hui Lu, Xuemin Feng, Ting Du, Jianhua Li, Qiang Zhang, Xindong Gu, Yuandong Shao, Xingzhi Jing, Cheng Su","doi":"10.3892/ijmm.2023.5339","DOIUrl":"https://doi.org/10.3892/ijmm.2023.5339","url":null,"abstract":"Iron overload and ferroptosis are associated with intervertebral disc degeneration (IDD); however, the mechanism underlying the regulation of iron homeostasis remains to be elucidated. Nuclear factor erythroid 2‑related factor 2 (Nrf2) has been reported to regulate cellular iron homeostasis; however, its impact on IDD pathology and the underlying mechanism of action requires further investigation. In the present study, immunohistochemistry analysis of Nrf2 expression in the cartilage endplate (CEP) was conducted and it was demonstrated that Nrf2 expression was increased in the CEP at the early stages of the development of IDD, whereas it was decreased at the late stages of the development of IDD. The results of western blot analysis indicated that the inadequate activation of Nrf2 may aggravate mitochondrial dysfunction and oxidative stress, thus promoting CEP chondrocyte degeneration and calcification. It was also revealed that Nrf2 was involved in TNF‑α‑induced CEP chondrocyte iron metabolism dysfunction and ferroptosis. Inhibition of Nrf2 expression using Nrf2 small interfering RNA could enhance the process of nuclear receptor coactivator 4 (NCOA4)‑mediated ferritinophagy and increase ferrous ion content, which may promote CEP chondrocyte ferroptotic cell death and extracellular matrix degradation. Furthermore, a decrease in cellular iron concentration may inhibit CEP chondrocyte ferroptosis, and CEP degeneration and calcification. The present study highlights the role of the Nrf2/NCOA4 axis in chondrocyte ferroptosis and IDD pathogenesis, thus suggesting that activation of Nrf2 may be a promising strategy for IDD treatment.","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138560161","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":"Emerging nanomaterials targeting macrophage adapted to abnormal metabolism in cancer and atherosclerosis therapy (Review).","authors":"Miaomiao Xu, Ying Cui, Siyuan Wei, Xuelong Cong, Yiying Chen, Shujie Tian, Anqi Yao, Weiwei Chen, Lixing Weng","doi":"10.3892/ijmm.2023.5337","DOIUrl":"https://doi.org/10.3892/ijmm.2023.5337","url":null,"abstract":"Macrophages, as highly heterogeneous and plastic immune cells, occupy a pivotal role in both pro‑inflammatory (M1) and anti‑inflammatory (M2) responses. While M1‑type macrophages secrete pro‑inflammatory factors to initiate and sustain inflammation, M2‑type macrophages promote inflammation regression and uphold tissue homeostasis. These distinct phenotypic transitions in macrophages are closely linked to significant alterations in cellular metabolism, encompassing key response pathways such as glycolysis, pentose phosphate pathway, oxidative phosphorylation, lipid metabolism, amino acid metabolism, the tricarboxylic acid cycle and iron metabolism. These metabolic adaptations enable macrophages to adapt their activities in response to varying disease microenvironments. Therefore, the present review focused primarily on elucidating the intricate metabolic pathways that underlie macrophage functionality. Subsequently, it offers a comprehensive overview of the current state‑of‑the‑art nanomaterials, highlighting their promising potential in modulating macrophage metabolism to effectively hinder disease progression in both cancer and atherosclerosis.","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138560178","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}