International journal of molecular medicine最新文献

{"title":"Anthrahydroquinone‑2,6‑disulfonate attenuates PQ‑induced acute lung injury through decreasing pulmonary microvascular permeability via inhibition of the PI3K/AKT/eNOS pathway.","authors":"Nan Li, Yang Yi, Jun Chen, Yue Huang, Jichao Peng, Zhao Li, Ying Wang, Jiadong Zhang, Chaoqun Xu, Haoran Liu, Jinghua Li, Xiaoran Liu","doi":"10.3892/ijmm.2024.5387","DOIUrl":"10.3892/ijmm.2024.5387","url":null,"abstract":"<p><p>In paraquat (PQ)‑induced acute lung injury (ALI)/ acute respiratory distress syndrome, PQ disrupts endothelial cell function and vascular integrity, which leads to increased pulmonary leakage. Anthrahydroquinone‑2,6‑disulfonate (AH2QDS) is a reducing agent that attenuates the extent of renal injury and improves survival in PQ‑intoxicated Sprague‑Dawley (SD) rats. The present study aimed to explore the beneficial role of AH2QDS in PQ‑induced ALI and its related mechanisms. A PQ‑intoxicated ALI model was established using PQ gavage in SD rats. Human pulmonary microvascular endothelial cells (HPMECs) were challenged with PQ. Superoxide dismutase, malondialdehyde, reactive oxygen species and nitric oxide (NO) fluorescence were examined to detect the level of oxidative stress in HPMECs. The levels of TNF‑α, IL‑1β and IL‑6 were assessed using an ELISA. Transwell and Cell Counting Kit‑8 assays were performed to detect the migration and proliferation of the cells. The pathological changes in lung tissues and blood vessels were examined by haematoxylin and eosin staining. Evans blue staining was used to detect pulmonary microvascular permeability. Western blotting was performed to detect target protein levels. Immunofluorescence and immunohistochemical staining were used to detect the expression levels of target proteins in HPMECs and lung tissues. AH2QDS inhibited inflammatory responses in lung tissues and HPMECs, and promoted the proliferation and migration of HPMECs. In addition, AH2QDS reduced pulmonary microvascular permeability by upregulating the levels of vascular endothelial‑cadherin, zonula occludens‑1 and CD31, thereby attenuating pathological changes in the lungs in rats. Finally, these effects may be related to the suppression of the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (AKT)/endothelial‑type NO synthase (eNOS) signalling pathway in endothelial cells. In conclusion, AH2QDS ameliorated PQ‑induced ALI by improving alveolar endothelial barrier disruption via modulation of the PI3K/AKT/eNOS signalling pathway, which may be an effective candidate for the treatment of PQ‑induced ALI.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317257","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":"Public neoantigens in breast cancer immunotherapy (Review).","authors":"Natthaporn Sueangoen, Peti Thuwajit, Pa-Thai Yenchitsomanus, Chanitra Thuwajit","doi":"10.3892/ijmm.2024.5388","DOIUrl":"10.3892/ijmm.2024.5388","url":null,"abstract":"<p><p>Among women globally, breast cancer is the most prevalent cancer and the leading cause of cancer‑related death. Interestingly, though genetic mutations contribute to the disease, <15% of women diagnosed with breast cancer have a family history of the disease, suggesting a prevalence of sporadic genetic mutations in breast cancer development. In the rapidly rising field of cancer genomics, neoantigen‑based immunotherapy has come to the fore. The investigation of novel proteins arising from unique somatic mutations or neoantigens have opened a new pathway for both individualized and public cancer treatments. Because they are shared among individuals with similar genetic changes, public neoantigens provide an opportunity for 'off‑the‑shelf' anticancer therapies, potentially extending the benefits to a wider patient group. The present review aimed to highlight the role of shared or public neoantigens as therapeutic targets for patients with breast cancer, emphasizing common hotspot mutations of certain genes identified in breast cancer. The clinical utilization of public neoantigen‑based therapies for breast cancer treatment were also discussed.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"54 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431939","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":"Effects of DNA methylation and its application in inflammatory bowel disease (Review).","authors":"Francis Atim Akanyibah, Yi Zhu, Aijun Wan, Dickson Kofi Wiredu Ocansey, Yuxuan Xia, An-Ning Fang, Fei Mao","doi":"10.3892/ijmm.2024.5379","DOIUrl":"10.3892/ijmm.2024.5379","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is marked by persistent inflammation, and its development and progression are linked to environmental, genetic, immune system and gut microbial factors. DNA methylation (DNAm), as one of the protein modifications, is a crucial epigenetic process used by cells to control gene transcription. DNAm is one of the most common areas that has drawn increasing attention recently, with studies revealing that the interleukin (IL)‑23/IL‑12, wingless‑related integration site, IL‑6‑associated signal transducer and activator of transcription 3, suppressor of cytokine signaling 3 and apoptosis signaling pathways are involved in DNAm and in the pathogenesis of IBD. It has emerged that DNAm‑associated genes are involved in perpetuating the persistent inflammation that characterizes a number of diseases, including IBD, providing a novel therapeutic strategy for exploring their treatment. The present review discusses DNAm‑associated genes in the pathogenesis of IBD and summarizes their application as possible diagnostic, prognostic and therapeutic biomarkers in IBD. This may provide a reference for the particular form of IBD and its related methylation genes, aiding in clinical decision‑making and encouraging therapeutic alternatives.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"53 6","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856314","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":"Predictive DNA damage signaling for low‑dose ionizing radiation.","authors":"Jeong-In Park, Seung-Youn Jung, Kyung-Hee Song, Dong-Hyeon Lee, Jiyeon Ahn, Sang-Gu Hwang, In-Su Jung, Dae-Seog Lim, Jie-Young Song","doi":"10.3892/ijmm.2024.5380","DOIUrl":"10.3892/ijmm.2024.5380","url":null,"abstract":"<p><p>Numerous studies have attempted to develop biological markers for the response to radiation for broad and straightforward application in the field of radiation. Based on a public database, the present study selected several molecules involved in the DNA damage repair response, cell cycle regulation and cytokine signaling as promising candidates for low‑dose radiation‑sensitive markers. The HuT 78 and IM‑9 cell lines were irradiated in a concentration‑dependent manner, and the expression of these molecules was analyzed using western blot analysis. Notably, the activation of ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHK2), p53 and H2A histone family member X (H2AX) significantly increased in a concentration‑dependent manner, which was also observed in human peripheral blood mononuclear cells. To determine the radioprotective effects of cinobufagin, as an ATM and CHK2 activator, an <i>in vivo</i> model was employed using sub‑lethal and lethal doses in irradiated mice. Treatment with cinobufagin increased the number of bone marrow cells in sub‑lethal irradiated mice, and slightly elongated the survival of lethally irradiated mice, although the difference was not statistically significant. Therefore, KU60019, BML‑277, pifithrin‑α, and nutlin‑3a were evaluated for their ability to modulate radiation‑induced cell death. The use of BML‑277 led to a decrease in radiation‑induced p‑CHK2 and γH2AX levels and mitigated radiation‑induced apoptosis. On the whole, the present study provides a novel approach for developing drug candidates based on the profiling of biological radiation‑sensitive markers. These markers hold promise for predicting radiation exposure and assessing the associated human risk.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"53 6","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862171","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":"Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review).","authors":"Shan Chong, Guangyan Mu, Xinan Cen, Qian Xiang, Yimin Cui","doi":"10.3892/ijmm.2024.5381","DOIUrl":"10.3892/ijmm.2024.5381","url":null,"abstract":"<p><p>Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are widely recognised as being able to induce a potent reduction in low‑density lipoprotein‑cholesterol. An increasing number of studies have suggested that PCSK9 also influences the haemostatic system by altering platelet function and the coagulation cascade. These findings have significant implications for anti‑PCSK9 therapy in patients with specific coagulation conditions, including expanded indications, dose adjustments and drug interactions. The present review summarises the changes in PCSK9 levels in individuals with liver diseases, chronic kidney diseases, diabetes mellitus, cancer and other disease states, and discusses their impact on thrombosis and haemostasis. Furthermore, the structure, effects and regulatory mechanisms of PCSK9 on platelets, coagulation factors, inflammatory cells and endothelial cells during coagulation and haemostasis are described.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"53 6","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957181","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 circular RNA as competing endogenous RNA in ovarian cancer (Review).","authors":"Wanlu Ye, Nan Xiang, Qing Wang, Yanming Lu","doi":"10.3892/ijmm.2024.5365","DOIUrl":"10.3892/ijmm.2024.5365","url":null,"abstract":"<p><p>Circular RNA (circRNA), a type of non‑coding RNA, plays a regulatory role in biological processes. The special loop structure of circRNA makes it highly stable and specific in diseased tissues and cells, especially in tumors. Competing endogenous RNAs (ceRNAs) compete for the binding of microRNA (miRNA) at specific binding sites and thus regulate gene expression. ceRNAs play an important role in various diseases and are currently recognized as the most prominent mechanism of action of circRNAs. circRNAs can modulate the proliferation, migration, invasion and apoptosis of tumor cells through the ceRNA mechanism. With further research, circRNAs may serve as novel markers and therapeutic targets for ovarian cancer (OC). In the present review, the research progress of circRNAs as ceRNAs in OC was summarized, focusing on the effects of the circRNA/miRNA/mRNA axis on the biological functions of OC cells through mediating pivotal signaling pathways. The role of circRNAs in the diagnosis, prognostic assessment and treatment of OC was also discussed in the present review.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"53 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059317","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":"Circular RNAs and the regulation of gene expression in diabetic nephropathy (Review).","authors":"Maximo Berto Martinez Benitez, Yussel Pérez Navarro, Elisa Azuara-Liceaga, Angeles Tecalco Cruz, Jesús Valdés Flores, Lilia Lopez-Canovas","doi":"10.3892/ijmm.2024.5368","DOIUrl":"10.3892/ijmm.2024.5368","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are non‑coding single‑stranded covalently closed RNA molecules that are considered important as regulators of gene expression at the transcriptional and post‑transcriptional levels. These molecules have been implicated in the initiation and progression of multiple human diseases, ranging from cancer to inflammatory and metabolic diseases, including diabetes mellitus and its vascular complications. The present article aimed to review the current knowledge on the biogenesis and functions of circRNAs, as well as their role in cell processes associated with diabetic nephropathy. In addition, novel potential interactions between circRNAs expressed in renal cells exposed to high‑glucose concentrations and the transcription factors c‑Jun and c‑Fos are reported.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"53 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184416","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 microglia/macrophage polarisation in intraocular diseases (Review).","authors":"Haoran Li, Biao Li, Yanlin Zheng","doi":"10.3892/ijmm.2024.5369","DOIUrl":"10.3892/ijmm.2024.5369","url":null,"abstract":"<p><p>Macrophages form a crucial component of the innate immune system, and their activation is indispensable for various aspects of immune and inflammatory processes, tissue repair, and maintenance of the balance of the body's state. Macrophages are found in all ocular tissues, spanning from the front surface, including the cornea, to the posterior pole, represented by the choroid/sclera. The neural retina is also populated by specialised resident macrophages called microglia. The plasticity of microglia/macrophages allows them to adopt different activation states in response to changes in the tissue microenvironment. When exposed to various factors, microglia/macrophages polarise into distinct phenotypes, each exhibiting unique characteristics and roles. Furthermore, extensive research has indicated a close association between microglia/macrophage polarisation and the development and reversal of various intraocular diseases. The present article provides a review of the recent findings on the association between microglia/macrophage polarisation and ocular pathological processes (including autoimmune uveitis, optic neuritis, sympathetic ophthalmia, retinitis pigmentosa, glaucoma, proliferative vitreoretinopathy, subretinal fibrosis, uveal melanoma, ischaemic optic neuropathy, retinopathy of prematurity and choroidal neovascularization). The paradoxical role of microglia/macrophage polarisation in retinopathy of prematurity is also discussed. Several studies have shown that microglia/macrophages are involved in the pathology of ocular diseases. However, it is required to further explore the relevant mechanisms and regulatory processes. The relationship between the functional diversity displayed by microglia/macrophage polarisation and intraocular diseases may provide a new direction for the treatment of intraocular diseases.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"53 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318249","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":"Methylation‑sensitive restriction enzyme‑droplet digital PCR assay for the one‑step highly sensitive analysis of DNA methylation hotspots.","authors":"Giuseppe Gattuso, Alessandro Lavoro, Rosario Caltabiano, Gabriele Madonna, Mariaelena Capone, Paolo Antonio Ascierto, Luca Falzone, Massimo Libra, Saverio Candido","doi":"10.3892/ijmm.2024.5366","DOIUrl":"10.3892/ijmm.2024.5366","url":null,"abstract":"<p><p>DNA methylation is an epigenetic modification that plays a key role in several cellular processes mediating the fine regulation of gene expression. Aberrant DNA methylation is observed in a wide range of pathologies, including cancer. Since these DNA modifications are transferred to the cell progenies and are stable over the time, the analysis of DNA methylation status has been proposed for diagnostic and prognostic purposes in cancer. Currently, DNA bisulfite conversion is the gold standard method for the high‑throughput analysis of DNA methylation alterations. However, bisulfite treatment induces DNA fragmentation affecting its quality for the downstream analyses. In this field, it is mandatory to identify novel methods to overcome the limits of conventional approaches. In the present study, the Methylation‑Sensitive Restriction Enzyme‑droplet digital PCR (MSRE‑ddPCR) assay was developed as a novel sensitive method for the analysis of DNA methylation of short genomic regions, combining the MSRE assay with the high‑sensitivity ddPCR and using an exogenous methylation sequence as control. Setup and validation experiments were performed analyzing a methylation hotspot of the <i>Solute Carrier Family 22 Member 17</i> in DNA samples derived from melanoma cell lines as well as from tissues and serum samples obtained from patients with melanoma and healthy controls. Compared with the standard MSRE approaches, the MSRE‑ddPCR assay is more appropriate for the analysis of DNA methylation (methDNA) in samples with low amounts of DNA (up to 0.651 ng) showing a greater sensitivity. These findings suggested the potential clinical application of MSRE‑ddPCR paving the way to the analysis of other methDNA hotspots in different tumors.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"53 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131371","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] Sulforaphane regulates apoptosis‑ and proliferation‑related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer.","authors":"Shi-Feng Kan, Jian Wang, Guan-Xing Sun","doi":"10.3892/ijmm.2024.5367","DOIUrl":"10.3892/ijmm.2024.5367","url":null,"abstract":"<p><p>Following the publication of this paper, the authors realized that they had made an error in assembling the data shown in Fig. 6B on p. 2455, and requested the publication of a corrigendum to rectify this error. However, following an independent investigation of the data published in this paper made by the Editorial Office, it was noted that one set of the immunofluorescence assay images shown in Fig. 4A appeared to be strikingly similar to data appearing in different form in a paper published previously in the journal <i>BMC Medicine</i> by different authors at different research institutes [Jing Y‑Y, Han Z‑P, Sun K, Zhang S‑S, Hou J, Liu Y, Li R, Gao L, Zhao X, Zhao Q‑D et al: Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK‑Mff signaling pathways. BMC Medicine 10: 98, 2012]. Owing to the fact that the abovementioned data in Fig. 4A had already been published prior to its submission to <i>International Journal of Molecular Medicine</i>, the Editor has chosen to decline the authors' request to publish a corrigendum, and decided that this paper should be retracted from the Journal instead. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 2447‑2458, 2018; DOI: 10.3892/ijmm.2018.3860].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"53 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184415","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}