Osteocyte function is critical for metabolism, remodelling and regeneration of bone tissue. In the present study, the roles of regulator of G protein signalling 18 (RGS18) were assessed in the regulation of osteocyte proliferation and bone formation. Target genes and signalling pathways were screened using the Gene Expression Omnibus (GEO) database and Gene Set Enrichment Analysis (GSEA). The function of RGS18 and the associated mechanisms were analysed by Cell Counting Kit 8 assay, 5‑ethynyl‑2'‑deoxyuridine assay, flow cytometry, reverse transcription‑quantitative PCR, western blotting and immunostaining. Overlap analysis of acutely injured subjects (AIS) and healthy volunteers (HVs) from the GSE93138 and GSE93215 datasets of the GEO database identified four genes: KIAA0825, ANXA3, RGS18 and LIPN. Notably, RGS18 was more highly expressed in peripheral blood samples from AIS than in those from HVs. Furthermore, RGS18 overexpression promoted MLO‑Y4 and MC3T3‑E1 cell viability, proliferation and S‑phase arrest, but inhibited apoptosis by suppressing caspase‑3/9 cleavage. Silencing RGS18 exerted the opposite effects. GSEA of GSE93138 revealed that RGS18 has the ability to regulate MAPK signalling. Treatment with the MEK1/2 inhibitor PD98059 reversed the RGS18 overexpression‑induced osteocyte proliferation, and treatment with the ERK1/2 activator 12‑O‑tetradecanoylphorbol‑13‑acetate reversed the effects of RGS18 silencing on osteocyte proliferation. In conclusion, RGS18 may contribute to osteocyte proliferation and bone fracture healing via activation of ERK signalling.
{"title":"Regulator of G protein signalling 18 promotes osteocyte proliferation by activating the extracellular signal‑regulated kinase signalling pathway.","authors":"Yong Meng, Si-Qiang Qiu, Qiang Wang, Jin-Liang Zuo","doi":"10.3892/ijmm.2024.5346","DOIUrl":"10.3892/ijmm.2024.5346","url":null,"abstract":"<p><p>Osteocyte function is critical for metabolism, remodelling and regeneration of bone tissue. In the present study, the roles of regulator of G protein signalling 18 (RGS18) were assessed in the regulation of osteocyte proliferation and bone formation. Target genes and signalling pathways were screened using the Gene Expression Omnibus (GEO) database and Gene Set Enrichment Analysis (GSEA). The function of RGS18 and the associated mechanisms were analysed by Cell Counting Kit 8 assay, 5‑ethynyl‑2'‑deoxyuridine assay, flow cytometry, reverse transcription‑quantitative PCR, western blotting and immunostaining. Overlap analysis of acutely injured subjects (AIS) and healthy volunteers (HVs) from the GSE93138 and GSE93215 datasets of the GEO database identified four genes: <i>KIAA0825</i>, <i>ANXA3</i>, <i>RGS18</i> and <i>LIPN</i>. Notably, <i>RGS18</i> was more highly expressed in peripheral blood samples from AIS than in those from HVs. Furthermore, <i>RGS18</i> overexpression promoted MLO‑Y4 and MC3T3‑E1 cell viability, proliferation and S‑phase arrest, but inhibited apoptosis by suppressing caspase‑3/9 cleavage. Silencing <i>RGS18</i> exerted the opposite effects. GSEA of GSE93138 revealed that RGS18 has the ability to regulate MAPK signalling. Treatment with the MEK1/2 inhibitor PD98059 reversed the <i>RGS18</i> overexpression‑induced osteocyte proliferation, and treatment with the ERK1/2 activator 12‑O‑tetradecanoylphorbol‑13‑acetate reversed the effects of RGS18 silencing on osteocyte proliferation. In conclusion, RGS18 may contribute to osteocyte proliferation and bone fracture healing via activation of ERK signalling.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10836495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424626","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}
Pub Date : 2024-03-01Epub Date: 2024-01-19DOI: 10.3892/ijmm.2024.5349
Hong Zhou, Qun Zhang, Chenyang Liu, Jiahao Fan, Wen Huang, Nan Li, Mingxia Yang, Hong Wang, Weiping Xie, Hui Kong
NOD-like receptor protein 3 (NLRP3) inflammasome is closely related to silica particle‑induced chronic lung inflammation but its role in epithelial remodeling, repair and regeneration in the distal lung during development of silicosis remains to be elucidated. The present study aimed to determine the effects of the NLRP3 inflammasome on epithelial remodeling and cellular regeneration and potential mechanisms in the distal lung of silica‑treated mice at three time points. Pulmonary function assessment, inflammatory cell counting, enzyme‑linked immunosorbent assay, histological and immunological analyses, hydroxyproline assay and western blotting were used in the study. Single intratracheal instillation of a silica suspension caused sustained NLRP3 inflammasome activation in the distal lung. Moreover, a time‑dependent increase in airway resistance and a decrease in lung compliance accompanied progression of pulmonary fibrosis. In the terminal bronchiole, lung remodeling including pyroptosis (membrane‑distributed GSDMD+), excessive proliferation (Ki67+), mucus overproduction (mucin 5 subtype AC and B) and epithelial‑mesenchymal transition (decreased E‑Cadherin+ and increased Vimentin+), was observed by immunofluorescence analysis. Notably, aberrant spatiotemporal expression of the embryonic lung stem/progenitor cell markers SOX2 and SOX9 and ectopic distribution of bronchioalveolar stem cells were observed in the distal lung only on the 7th day after silica instillation (the early inflammatory phase of silicosis). Western blotting revealed that the Sonic hedgehog/Glioma‑associated oncogene (Shh/Gli) and Wnt/β‑catenin pathways were involved in NLRP3 inflammasome activation‑mediated epithelial remodeling and dysregulated regeneration during the inflammatory and fibrotic phases. Overall, sustained NLRP3 inflammasome activation led to epithelial remodeling in the distal lung of mice. Moreover, understanding the spatiotemporal profile of dysregulated epithelial repair and regeneration may provide a novel therapeutic strategy for inhalable particle‑related chronic inflammatory and fibrotic lung disease.
NOD样受体蛋白3(NLRP3)炎性体与二氧化硅颗粒诱导的慢性肺部炎症密切相关,但它在矽肺发展过程中远端肺上皮重塑、修复和再生中的作用仍有待阐明。本研究旨在确定 NLRP3 炎性体在三个时间点对二氧化硅处理小鼠远端肺上皮重塑和细胞再生的影响及潜在机制。研究采用了肺功能评估、炎性细胞计数、酶联免疫吸附试验、组织学和免疫学分析、羟脯氨酸测定和 Western 印迹等方法。气管内单次灌入二氧化硅悬浮液可导致远端肺部 NLRP3 炎症小体持续活化。此外,气道阻力的增加和肺顺应性的降低与肺纤维化的进展呈时间依赖性。在终末支气管中,通过免疫荧光分析观察到肺部重塑,包括热变态反应(膜分布的 GSDMD+)、过度增殖(Ki67+)、粘液过度分泌(粘蛋白 5 亚型 AC 和 B)和上皮-间质转化(E-Cadherin+ 减少,Vimentin+ 增加)。值得注意的是,仅在二氧化硅灌入后第7天(矽肺早期炎症阶段),远端肺部才观察到胚胎肺干/祖细胞标志物SOX2和SOX9的时空异常表达以及支气管肺泡干细胞的异位分布。Western blotting显示,在炎症期和纤维化期,Sonic hedgehog/Glioma-associated oncogene (Shh/Gli) 和Wnt/β-catenin通路参与了NLRP3炎性体激活介导的上皮重塑和再生失调。总体而言,NLRP3炎性体的持续激活导致了小鼠远端肺上皮重塑。此外,了解上皮修复和再生失调的时空概况可能会为与可吸入颗粒相关的慢性炎症和纤维化肺病提供一种新的治疗策略。
{"title":"NLRP3 inflammasome mediates abnormal epithelial regeneration and distal lung remodeling in silica‑induced lung fibrosis.","authors":"Hong Zhou, Qun Zhang, Chenyang Liu, Jiahao Fan, Wen Huang, Nan Li, Mingxia Yang, Hong Wang, Weiping Xie, Hui Kong","doi":"10.3892/ijmm.2024.5349","DOIUrl":"10.3892/ijmm.2024.5349","url":null,"abstract":"<p><p>NOD-like receptor protein 3 (NLRP3) inflammasome is closely related to silica particle‑induced chronic lung inflammation but its role in epithelial remodeling, repair and regeneration in the distal lung during development of silicosis remains to be elucidated. The present study aimed to determine the effects of the NLRP3 inflammasome on epithelial remodeling and cellular regeneration and potential mechanisms in the distal lung of silica‑treated mice at three time points. Pulmonary function assessment, inflammatory cell counting, enzyme‑linked immunosorbent assay, histological and immunological analyses, hydroxyproline assay and western blotting were used in the study. Single intratracheal instillation of a silica suspension caused sustained NLRP3 inflammasome activation in the distal lung. Moreover, a time‑dependent increase in airway resistance and a decrease in lung compliance accompanied progression of pulmonary fibrosis. In the terminal bronchiole, lung remodeling including pyroptosis (membrane‑distributed GSDMD<sup>+</sup>), excessive proliferation (Ki67<sup>+</sup>), mucus overproduction (mucin 5 subtype AC and B) and epithelial‑mesenchymal transition (decreased E‑Cadherin<sup>+</sup> and increased Vimentin<sup>+</sup>), was observed by immunofluorescence analysis. Notably, aberrant spatiotemporal expression of the embryonic lung stem/progenitor cell markers SOX2 and SOX9 and ectopic distribution of bronchioalveolar stem cells were observed in the distal lung only on the 7th day after silica instillation (the early inflammatory phase of silicosis). Western blotting revealed that the Sonic hedgehog/Glioma‑associated oncogene (Shh/Gli) and Wnt/β‑catenin pathways were involved in NLRP3 inflammasome activation‑mediated epithelial remodeling and dysregulated regeneration during the inflammatory and fibrotic phases. Overall, sustained NLRP3 inflammasome activation led to epithelial remodeling in the distal lung of mice. Moreover, understanding the spatiotemporal profile of dysregulated epithelial repair and regeneration may provide a novel therapeutic strategy for inhalable particle‑related chronic inflammatory and fibrotic lung disease.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10836498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491406","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}
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 3A and B on p. 1306 were strikingly similar to data appearing in different form in a paper by different authors at a different research institute that had already been submitted for publication. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. 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 46: 1301‑1310, 2020; DOI: 10.3892/ijmm.2020.4704].
{"title":"[Retracted] MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells.","authors":"Xu Chen, Ruiqin Cao, Haifang Liu, Tuanying Zhang, Xinrong Yuan, Shuxiang Xu","doi":"10.3892/ijmm.2024.5348","DOIUrl":"10.3892/ijmm.2024.5348","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 3A and B on p. 1306 were strikingly similar to data appearing in different form in a paper by different authors at a different research institute that had already been submitted for publication. Owing to the fact that the contentious data in the above article had already been submitted for publication 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. 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 46: 1301‑1310, 2020; DOI: 10.3892/ijmm.2020.4704].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10836516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491402","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}
Pub Date : 2024-03-01Epub Date: 2024-02-01DOI: 10.3892/ijmm.2024.5354
Yifeng Zhang, Hang Yang, Shuai Hou, Yulei Xia, Yan-Qiang Wang
Stroke, a debilitating cerebrovascular ailment, poses significant threats to human life and health. The intricate interplay between the gut‑brain‑microbiota axis (GBMA) and cerebral ischemia‑reperfusion has increasingly become a focal point of scientific exploration, emerging as a pivotal research avenue in stroke pathophysiology. In the present review, the authors delved into the nexus between the GBMA and neuroinflammation observed post‑stroke. The analysis underscored the pivotal roles of histone deacetylase 3 and neutrophil extracellular traps subsequent to stroke incidents. The influence of gut microbial compositions and their metabolites, notably short‑chain fatty acids and trimethylamine N‑oxide, on neuroinflammatory processes, was further elucidated. The involvement of immune cells, especially regulatory T‑cells, and the intricate signaling cascades including cyclic GMP‑AMP synthase/stimulator of interferon genes/Toll‑like receptor, further emphasized the complex regulatory mechanisms of GBMA in cerebral ischemia/reperfusion injury (CI/RI). Collectively, the present review offered a comprehensive perspective on the metabolic, immune and inflammatory modulations orchestrated by GBMA, augmenting the understanding of its role in neuroinflammation following CI/RI.
{"title":"Influence of the brain‑gut axis on neuroinflammation in cerebral ischemia‑reperfusion injury (Review).","authors":"Yifeng Zhang, Hang Yang, Shuai Hou, Yulei Xia, Yan-Qiang Wang","doi":"10.3892/ijmm.2024.5354","DOIUrl":"10.3892/ijmm.2024.5354","url":null,"abstract":"<p><p>Stroke, a debilitating cerebrovascular ailment, poses significant threats to human life and health. The intricate interplay between the gut‑brain‑microbiota axis (GBMA) and cerebral ischemia‑reperfusion has increasingly become a focal point of scientific exploration, emerging as a pivotal research avenue in stroke pathophysiology. In the present review, the authors delved into the nexus between the GBMA and neuroinflammation observed post‑stroke. The analysis underscored the pivotal roles of histone deacetylase 3 and neutrophil extracellular traps subsequent to stroke incidents. The influence of gut microbial compositions and their metabolites, notably short‑chain fatty acids and trimethylamine N‑oxide, on neuroinflammatory processes, was further elucidated. The involvement of immune cells, especially regulatory T‑cells, and the intricate signaling cascades including cyclic GMP‑AMP synthase/stimulator of interferon genes/Toll‑like receptor, further emphasized the complex regulatory mechanisms of GBMA in cerebral ischemia/reperfusion injury (CI/RI). Collectively, the present review offered a comprehensive perspective on the metabolic, immune and inflammatory modulations orchestrated by GBMA, augmenting the understanding of its role in neuroinflammation following CI/RI.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10852013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650751","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}
Pub Date : 2024-02-01Epub Date: 2023-12-22DOI: 10.3892/ijmm.2023.5341
Yu Zhou, Qiang Wu, Yingchu Guo
Atherosclerosis, a dominant driving force underlying multiple cardiovascular events, is an intertwined and chronic inflammatory disease characterized by lipid deposition in the arterial wall, which leads to diverse cardiovascular problems. Despite unprecedented advances in understanding the pathogenesis of atherosclerosis and the substantial decline in cardiovascular mortality, atherosclerotic cardiovascular disease remains a global public health issue. Understanding the molecular landscape of atherosclerosis is imperative in the field of molecular cardiology. Recently, compelling evidence has shown that an important family of homeobox (HOX) genes endows causality in orchestrating the interplay between various cardiovascular biological processes and atherosclerosis. Despite seemingly scratching the surface, such insight into the realization of biology promises to yield extraordinary breakthroughs in ameliorating atherosclerosis. Primarily recapitulated herein are the contributions of HOX in atherosclerosis, including diverse cardiovascular biology, knowledge gaps, remaining challenges and future directions. A snapshot of other cardiovascular biological processes was also provided, including cardiac/vascular development, cardiomyocyte pyroptosis/apoptosis, cardiac fibroblast proliferation and cardiac hypertrophy, which are responsible for cardiovascular disorders. Further in‑depth investigation of HOX promises to provide a potential yet challenging landscape, albeit largely undetermined to date, for partially pinpointing the molecular mechanisms of atherosclerosis. A plethora of new targeted therapies may ultimately emerge against atherosclerosis, which is rapidly underway. However, translational undertakings are crucially important but increasingly challenging and remain an ongoing and monumental conundrum in the field.
{"title":"Deciphering the emerging landscape of HOX genes in cardiovascular biology, atherosclerosis and beyond (Review).","authors":"Yu Zhou, Qiang Wu, Yingchu Guo","doi":"10.3892/ijmm.2023.5341","DOIUrl":"10.3892/ijmm.2023.5341","url":null,"abstract":"<p><p>Atherosclerosis, a dominant driving force underlying multiple cardiovascular events, is an intertwined and chronic inflammatory disease characterized by lipid deposition in the arterial wall, which leads to diverse cardiovascular problems. Despite unprecedented advances in understanding the pathogenesis of atherosclerosis and the substantial decline in cardiovascular mortality, atherosclerotic cardiovascular disease remains a global public health issue. Understanding the molecular landscape of atherosclerosis is imperative in the field of molecular cardiology. Recently, compelling evidence has shown that an important family of homeobox (HOX) genes endows causality in orchestrating the interplay between various cardiovascular biological processes and atherosclerosis. Despite seemingly scratching the surface, such insight into the realization of biology promises to yield extraordinary breakthroughs in ameliorating atherosclerosis. Primarily recapitulated herein are the contributions of HOX in atherosclerosis, including diverse cardiovascular biology, knowledge gaps, remaining challenges and future directions. A snapshot of other cardiovascular biological processes was also provided, including cardiac/vascular development, cardiomyocyte pyroptosis/apoptosis, cardiac fibroblast proliferation and cardiac hypertrophy, which are responsible for cardiovascular disorders. Further in‑depth investigation of HOX promises to provide a potential yet challenging landscape, albeit largely undetermined to date, for partially pinpointing the molecular mechanisms of atherosclerosis. A plethora of new targeted therapies may ultimately emerge against atherosclerosis, which is rapidly underway. However, translational undertakings are crucially important but increasingly challenging and remain an ongoing and monumental conundrum in the field.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10781420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829678","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}
Pub Date : 2024-02-01Epub Date: 2024-01-08DOI: 10.3892/ijmm.2024.5344
Maria I Zervou, Basil C Tarlatzis, Grigoris F Grimbizis, Demetrios A Spandidos, Timothy B Niewold, George N Goulielmos
Patients with a history of endometriosis have an increased risk of developing various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and celiac disease. There is a potential association between endometriosis and an increased susceptibility for Sjögren's syndrome (SS). SS is a common chronic, inflammatory, systemic, autoimmune, multifactorial disease of complex pathology, with genetic, epigenetic and environmental factors contributing to the development of this condition. It occurs in 0.5‑1% of the population, is characterized by the presence of ocular dryness, lymphocytic infiltrations and contributes to neurological, gastrointestinal, vascular and dermatological manifestations. Endometriosis is an inflammatory, estrogen‑dependent, multifactorial, heterogeneous gynecological disease, affecting ≤10% of reproductive‑age women. It is characterized by the occurrence of endometrial tissue outside the uterine cavity, mainly in the pelvic cavity, and is associated with pelvic pain, dysmenorrhea, deep dyspareunia and either subfertility or infertility. It is still unclear whether SS appears as a secondary response to endometriosis, or it is developed due to any potential shared mechanisms of these conditions. The aim of the present review was to explore further the biological basis only of the co‑occurrence of these disorders but not their association at clinical basis, focusing on the analysis of the partially shared genetic background between endometriosis and SS, and the clarification of the possible similarities in the underlying pathogenetic mechanisms and the relevant molecular pathways.
有子宫内膜异位症病史的患者罹患各种自身免疫性疾病的风险会增加,如类风湿性关节炎、强直性脊柱炎、系统性红斑狼疮、多发性硬化症和乳糜泻。子宫内膜异位症与斯约格伦综合征(SS)的易感性增加之间存在潜在联系。斯约格伦综合征是一种常见的慢性、炎症性、全身性、自身免疫性、多因素的复杂病理疾病,遗传、表观遗传和环境因素都会导致该病的发生。该病的发病率占总人口的 0.5%-1%,其特征是眼部干燥、淋巴细胞浸润,并伴有神经、胃肠、血管和皮肤表现。子宫内膜异位症是一种炎症性、雌激素依赖性、多因素、异质性妇科疾病,发病率≤10%的育龄妇女。其特点是子宫内膜组织发生在子宫腔以外,主要在盆腔,并伴有盆腔疼痛、痛经、深度痛经、不孕或不育。目前尚不清楚 SS 是否是子宫内膜异位症的继发反应,还是由于这两种疾病潜在的共同机制所致。本综述旨在进一步探讨这些疾病同时发生的生物学基础,而不是它们在临床基础上的关联,重点分析子宫内膜异位症和 SS 之间部分共享的遗传背景,并澄清潜在致病机制和相关分子通路中可能存在的相似之处。
{"title":"Association of endometriosis with Sjögren's syndrome: Genetic insights (Review).","authors":"Maria I Zervou, Basil C Tarlatzis, Grigoris F Grimbizis, Demetrios A Spandidos, Timothy B Niewold, George N Goulielmos","doi":"10.3892/ijmm.2024.5344","DOIUrl":"10.3892/ijmm.2024.5344","url":null,"abstract":"<p><p>Patients with a history of endometriosis have an increased risk of developing various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and celiac disease. There is a potential association between endometriosis and an increased susceptibility for Sjögren's syndrome (SS). SS is a common chronic, inflammatory, systemic, autoimmune, multifactorial disease of complex pathology, with genetic, epigenetic and environmental factors contributing to the development of this condition. It occurs in 0.5‑1% of the population, is characterized by the presence of ocular dryness, lymphocytic infiltrations and contributes to neurological, gastrointestinal, vascular and dermatological manifestations. Endometriosis is an inflammatory, estrogen‑dependent, multifactorial, heterogeneous gynecological disease, affecting ≤10% of reproductive‑age women. It is characterized by the occurrence of endometrial tissue outside the uterine cavity, mainly in the pelvic cavity, and is associated with pelvic pain, dysmenorrhea, deep dyspareunia and either subfertility or infertility. It is still unclear whether SS appears as a secondary response to endometriosis, or it is developed due to any potential shared mechanisms of these conditions. The aim of the present review was to explore further the biological basis only of the co‑occurrence of these disorders but not their association at clinical basis, focusing on the analysis of the partially shared genetic background between endometriosis and SS, and the clarification of the possible similarities in the underlying pathogenetic mechanisms and the relevant molecular pathways.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10781419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377558","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}
Ioannis Lempesis, V. Georgakopoulou, Russel Reiter, Demetrios A. Spandidos
{"title":"A mid‑pandemic night's dream: Melatonin, from harbinger of anti‑inflammation to mitochondrial savior in acute and long COVID‑19 (Review)","authors":"Ioannis Lempesis, V. Georgakopoulou, Russel Reiter, Demetrios A. Spandidos","doi":"10.3892/ijmm.2024.5352","DOIUrl":"https://doi.org/10.3892/ijmm.2024.5352","url":null,"abstract":"","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139595010","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}
Pub Date : 2024-01-01Epub Date: 2023-11-08DOI: 10.3892/ijmm.2023.5327
Xuehan Gao, Runying Long, Ming Qin, Wenfang Zhu, Linna Wei, Pinzhi Dong, Jin Chen, Junmin Luo, Jihong Feng
Tumor‑associated macrophages (TAMs) are pivotal components in colorectal cancer (CRC) progression, markedly influencing the tumor microenvironment through their polarization into the pro‑inflammatory M1 or pro‑tumorigenic M2 phenotypes. Recent studies have highlighted that the Grb2‑associated binder 2 (Gab2) is a critical gene involved in the development of various types of tumor, including CRC. However, the precise role of Gab2 in mediating TAM polarization remains incompletely elucidated. In the present study, it was discovered that Gab2 was highly expressed within CRC tissue TAMs, and was associated with a poor prognosis of patients with CRC. Functionally, it was identified that the tumor‑conditioned medium (TCM) induced Gab2 expression, facilitating the TAMs towards an M2‑like phenotype polarization. Of note, the suppression of Gab2 expression using shRNA markedly inhibited the TCM‑induced expression of M2‑associated molecules, without affecting M1‑type markers. Furthermore, the xenotransplantation model demonstrated that Gab2 deficiency in TAMs inhibited tumor growth in the mouse model of CRC. Mechanistically, Gab2 induced the M2 polarization of TAMs by regulating the AKT and ERK signaling pathways, promoting CRC growth and metastasis. In summary, the present study study elucidates that decreasing Gab2 expression hinders the transition of TAMs towards the M2 phenotype, thereby suppressing the growth of CRC. The exploration of the regulatory mechanisms of Gab2 in TAM polarization may enhance the current understanding of the core molecular pathways of CRC development and may thus provide a foundation for the development of novel immunotherapeutic strategies targeted against TAMs.
{"title":"Gab2 promotes the growth of colorectal cancer by regulating the M2 polarization of tumor‑associated macrophages.","authors":"Xuehan Gao, Runying Long, Ming Qin, Wenfang Zhu, Linna Wei, Pinzhi Dong, Jin Chen, Junmin Luo, Jihong Feng","doi":"10.3892/ijmm.2023.5327","DOIUrl":"10.3892/ijmm.2023.5327","url":null,"abstract":"<p><p>Tumor‑associated macrophages (TAMs) are pivotal components in colorectal cancer (CRC) progression, markedly influencing the tumor microenvironment through their polarization into the pro‑inflammatory M1 or pro‑tumorigenic M2 phenotypes. Recent studies have highlighted that the Grb2‑associated binder 2 (Gab2) is a critical gene involved in the development of various types of tumor, including CRC. However, the precise role of Gab2 in mediating TAM polarization remains incompletely elucidated. In the present study, it was discovered that Gab2 was highly expressed within CRC tissue TAMs, and was associated with a poor prognosis of patients with CRC. Functionally, it was identified that the tumor‑conditioned medium (TCM) induced Gab2 expression, facilitating the TAMs towards an M2‑like phenotype polarization. Of note, the suppression of Gab2 expression using shRNA markedly inhibited the TCM‑induced expression of M2‑associated molecules, without affecting M1‑type markers. Furthermore, the xenotransplantation model demonstrated that Gab2 deficiency in TAMs inhibited tumor growth in the mouse model of CRC. Mechanistically, Gab2 induced the M2 polarization of TAMs by regulating the AKT and ERK signaling pathways, promoting CRC growth and metastasis. In summary, the present study study elucidates that decreasing Gab2 expression hinders the transition of TAMs towards the M2 phenotype, thereby suppressing the growth of CRC. The exploration of the regulatory mechanisms of Gab2 in TAM polarization may enhance the current understanding of the core molecular pathways of CRC development and may thus provide a foundation for the development of novel immunotherapeutic strategies targeted against TAMs.</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/PMC10688767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481340","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}
Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration, secondary bone hyperplasia, inadequate extracellular matrix synthesis and degeneration of articular cartilage. Mesenchymal stem cells (MSCs) can self‑renew and undergo multidirectional differentiation; they can differentiate into chondrocytes. Aging MSCs have a weakened ability to differentiate, and release various pro‑inflammatory cytokines, which may contribute to OA progression; the other mechanism contributing to OA is epigenetic regulation (for instance, DNA methylation, histone modification and regulation of non‑coding RNA). Owing to the self‑renewal and differentiation ability of MSCs, various MSC‑based exogenous cell therapies have been developed to treat OA. The efficacy of MSC‑based therapy is mainly attributed to cytokines, growth factors and the paracrine effect of exosomes. Recently, extensive studies have been conducted on MSC‑derived exosomes. Exosomes from MSCs can deliver a variety of DNA, RNA, proteins and lipids, thereby facilitating MSC migration and cartilage repair. Therefore, MSC‑derived exosomes are considered a promising therapy for OA. The present review summarized the association between MSC aging and OA in terms of genetics and epigenetics, and characteristics of MSC‑derived exosomes, and the mechanism to alleviate OA cartilage damage.
{"title":"Single‑cell sequencing, genetics, and epigenetics reveal mesenchymal stem cell senescence in osteoarthritis (Review).","authors":"Dunyong Tan, Zeqi Huang, Zhe Zhao, Xiaoqiang Chen, Jianquan Liu, Daping Wang, Zhiqin Deng, Wencui Li","doi":"10.3892/ijmm.2023.5326","DOIUrl":"10.3892/ijmm.2023.5326","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration, secondary bone hyperplasia, inadequate extracellular matrix synthesis and degeneration of articular cartilage. Mesenchymal stem cells (MSCs) can self‑renew and undergo multidirectional differentiation; they can differentiate into chondrocytes. Aging MSCs have a weakened ability to differentiate, and release various pro‑inflammatory cytokines, which may contribute to OA progression; the other mechanism contributing to OA is epigenetic regulation (for instance, DNA methylation, histone modification and regulation of non‑coding RNA). Owing to the self‑renewal and differentiation ability of MSCs, various MSC‑based exogenous cell therapies have been developed to treat OA. The efficacy of MSC‑based therapy is mainly attributed to cytokines, growth factors and the paracrine effect of exosomes. Recently, extensive studies have been conducted on MSC‑derived exosomes. Exosomes from MSCs can deliver a variety of DNA, RNA, proteins and lipids, thereby facilitating MSC migration and cartilage repair. Therefore, MSC‑derived exosomes are considered a promising therapy for OA. The present review summarized the association between MSC aging and OA in terms of genetics and epigenetics, and characteristics of MSC‑derived exosomes, and the mechanism to alleviate OA cartilage damage.</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/PMC10688769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481341","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}
Pub Date : 2024-01-01Epub Date: 2023-12-01DOI: 10.3892/ijmm.2023.5331
Zuly A Sánchez-Florentino, Bianca S Romero-Martínez, Edgar Flores-Soto, Héctor Serrano, Luis M Montaño, Marcela Valdés-Tovar, Eduardo Calixto, Arnoldo Aquino-Gálvez, Germán O López-Riquelme, Ramón Alvarado, Jesús Argueta, Héctor Solís-Chagoyán, Bettina Sommer
Schizophrenia (SZ) is a multifactorial disorder characterized by volume reduction in gray and white matter, oxidative stress, neuroinflammation, altered neurotransmission, as well as molecular deficiencies such as punctual mutation in Disrupted‑in‑Schizophrenia 1 protein. In this regard, it is essential to understand the underlying molecular disturbances to determine the pathophysiological mechanisms of the disease. The signaling pathways activated by G protein‑coupled receptors (GPCRs) are key molecular signaling pathways altered in SZ. Convenient models need to be designed and validated to study these processes and mechanisms at the cellular level. Cultured olfactory stem cells are used to investigate neural molecular and cellular alterations related to the pathophysiology of SZ. Multipotent human olfactory stem cells are undifferentiated and express GPCRs involved in numerous physiological functions such as proliferation, differentiation and bioenergetics. The use of olfactory stem cells obtained from patients with SZ may identify alterations in GPCR signaling that underlie dysfunctional processes in both undifferentiated and specialized neurons or derived neuroglia. The present review aimed to analyze the role of GPCRs and their signaling in the pathophysiology of SZ. Culture of olfactory epithelial cells constitutes a suitable model to study SZ and other psychiatric disorders at the cellular level.
精神分裂症(SZ)是一种多因素疾病,其特征是灰质和白质体积减少、氧化应激、神经炎症、神经传递改变以及分子缺陷,如打乱- in - Schizophrenia - 1蛋白的准时突变。在这方面,有必要了解潜在的分子干扰,以确定疾病的病理生理机制。G蛋白偶联受体(gpcr)激活的信号通路是SZ发生改变的关键分子信号通路。需要设计和验证方便的模型来在细胞水平上研究这些过程和机制。利用培养的嗅觉干细胞研究与SZ病理生理相关的神经分子和细胞改变。多能性人嗅觉干细胞是一种未分化且表达gpcr的细胞,参与多种生理功能,如增殖、分化和生物能量学。使用从SZ患者获得的嗅觉干细胞可以识别GPCR信号的改变,这些改变是未分化和特化神经元或衍生神经胶质细胞功能障碍过程的基础。现就gpcr及其信号转导在SZ病理生理中的作用进行综述。嗅觉上皮细胞的培养是在细胞水平上研究SZ和其他精神疾病的合适模型。
{"title":"Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review).","authors":"Zuly A Sánchez-Florentino, Bianca S Romero-Martínez, Edgar Flores-Soto, Héctor Serrano, Luis M Montaño, Marcela Valdés-Tovar, Eduardo Calixto, Arnoldo Aquino-Gálvez, Germán O López-Riquelme, Ramón Alvarado, Jesús Argueta, Héctor Solís-Chagoyán, Bettina Sommer","doi":"10.3892/ijmm.2023.5331","DOIUrl":"10.3892/ijmm.2023.5331","url":null,"abstract":"<p><p>Schizophrenia (SZ) is a multifactorial disorder characterized by volume reduction in gray and white matter, oxidative stress, neuroinflammation, altered neurotransmission, as well as molecular deficiencies such as punctual mutation in Disrupted‑in‑Schizophrenia 1 protein. In this regard, it is essential to understand the underlying molecular disturbances to determine the pathophysiological mechanisms of the disease. The signaling pathways activated by G protein‑coupled receptors (GPCRs) are key molecular signaling pathways altered in SZ. Convenient models need to be designed and validated to study these processes and mechanisms at the cellular level. Cultured olfactory stem cells are used to investigate neural molecular and cellular alterations related to the pathophysiology of SZ. Multipotent human olfactory stem cells are undifferentiated and express GPCRs involved in numerous physiological functions such as proliferation, differentiation and bioenergetics. The use of olfactory stem cells obtained from patients with SZ may identify alterations in GPCR signaling that underlie dysfunctional processes in both undifferentiated and specialized neurons or derived neuroglia. The present review aimed to analyze the role of GPCRs and their signaling in the pathophysiology of SZ. Culture of olfactory epithelial cells constitutes a suitable model to study SZ and other psychiatric disorders at the cellular level.</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/PMC10712696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138459852","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}