Pregabalin and diclofenac diethylamine are anti-inflammatory molecules that are effective in relieving inflammation and pain associated with musculoskeletal disorders, arthritis, and post-traumatic pain, among others. Intravenous and oral delivery of these two molecules has their limitations. However, the transdermal route is believed to be an alternate viable option for the delivery of therapeutic molecules with desired physicochemical properties. To this end, it is vital to understand the physicochemical properties of these drugs, dosage, and strategies to enhance permeation, thereby surmounting the associated constraints and concurrently attaining a sustained release of these therapeutic molecules when administered in combination. The present work hypothesizes the enhanced permeation and sustained release of Pregabalin and diclofenac diethylamine across the skin, entrapped in the adhesive nano-organogel formulation, including permeation enhancers. The solubility studies of Pregabalin and diclofenac diethylamine in combination were performed in different permeation enhancers. Oleic acid was optimized as the best permeation enhancer based on in vitro studies. Pluronic organogel containing Pregabalin and diclofenac diethylamine with oleic acid was fabricated. Duro-Tak® (87-2196) was added to the organogel formulation as a pressure-sensitive adhesive to sustain the release profile of these two therapeutic molecules. The adhesive organogel was characterized for particle size, scanning electron microscopy, and contact angle measurement. The HPLC method developed for the quantification of the dual drug showed a retention time of 3.84 minutes and 9.69 minutes for pregabalin and diclofenac, respectively. The fabricated nanogel adhesive formulation showed the desired results with particle size and contact angle of 282 ± 57 nm and ≥120⁰, respectively. In vitro studies showed the percentage cumulative release of 24.90 ± 4.65% and 33.29 ± 4.81% for pregabalin and diclofenac, respectively. In order to accomplish transdermal permeation, the suggested hypothesis of fabricating PG and DEE nano-organogel in combination with permeation enhancers will be a viable drug delivery method. In comparison to a traditional gel formulation, oleic acid as a permeation enhancer increased the penetration of both PG and DEE from the organogel formulation. Notably, the studies showed that the use of pressure-sensitive adhesives enabled the sustained release of both PG and DEE.Therefore, the results anticipated the hypothesis that the transdermal delivery of adhesive PG and DEE-based nanogel across the human skin can be achieved to inhibit inflammation and pain.
普瑞巴林和双氯芬酸二乙胺是抗炎分子,可有效缓解肌肉骨骼疾病、关节炎和创伤后疼痛等引起的炎症和疼痛。这两种分子的静脉注射和口服给药都有其局限性。然而,透皮途径被认为是输送具有所需理化特性的治疗分子的另一种可行选择。为此,必须了解这些药物的理化特性、剂量和增强渗透的策略,从而克服相关的限制,同时在联合用药时实现这些治疗分子的持续释放。本研究假设普瑞巴林和双氯芬酸二乙胺在包括渗透促进剂在内的粘性纳米有机凝胶配方中的皮肤渗透和持续释放得到增强。在不同的渗透促进剂中对普瑞巴林和双氯芬酸二乙胺的溶解度进行了研究。根据体外研究,油酸被优化为最佳渗透促进剂。制造出了含有普瑞巴林和双氯芬酸二乙胺以及油酸的 Pluronic 有机凝胶。有机凝胶配方中添加了 Duro-Tak® (87-2196) 作为压敏粘合剂,以维持这两种治疗分子的释放曲线。对粘合剂有机凝胶的粒度、扫描电子显微镜和接触角测量进行了表征。为定量分析这两种药物而开发的高效液相色谱法显示,普瑞巴林和双氯芬酸的保留时间分别为 3.84 分钟和 9.69 分钟。所制备的纳米凝胶粘合剂配方的粒度和接触角分别为 282 ± 57 nm 和 ≥120⁰,达到了预期效果。体外研究显示,普瑞巴林和双氯芬酸的累积释放率分别为 24.90 ± 4.65% 和 33.29 ± 4.81%。为了实现透皮渗透,所提出的将 PG 和 DEE 纳米有机凝胶与渗透促进剂相结合的假设将是一种可行的给药方法。与传统的凝胶配方相比,油酸作为渗透促进剂可增加有机凝胶配方中 PG 和 DEE 的渗透。值得注意的是,研究表明,使用压敏粘合剂可以实现 PG 和 DEE 的持续释放。因此,研究结果提出了一个假设,即基于粘合剂的 PG 和 DEE 纳米凝胶可以通过人体皮肤实现透皮给药,从而抑制炎症和疼痛。
{"title":"Hypothesizing the Oleic Acid-Mediated Enhanced and Sustained Transdermal Codelivery of Pregabalin and Diclofenac Adhesive Nanogel: A Proof of Concept.","authors":"Deepanjan Datta, Afeefa Noor, Anjali Rathee, Snigdha Singh, Kanchan Kohli","doi":"10.2174/0115665240291343240306054318","DOIUrl":"https://doi.org/10.2174/0115665240291343240306054318","url":null,"abstract":"<p><p>Pregabalin and diclofenac diethylamine are anti-inflammatory molecules that are effective in relieving inflammation and pain associated with musculoskeletal disorders, arthritis, and post-traumatic pain, among others. Intravenous and oral delivery of these two molecules has their limitations. However, the transdermal route is believed to be an alternate viable option for the delivery of therapeutic molecules with desired physicochemical properties. To this end, it is vital to understand the physicochemical properties of these drugs, dosage, and strategies to enhance permeation, thereby surmounting the associated constraints and concurrently attaining a sustained release of these therapeutic molecules when administered in combination. The present work hypothesizes the enhanced permeation and sustained release of Pregabalin and diclofenac diethylamine across the skin, entrapped in the adhesive nano-organogel formulation, including permeation enhancers. The solubility studies of Pregabalin and diclofenac diethylamine in combination were performed in different permeation enhancers. Oleic acid was optimized as the best permeation enhancer based on in vitro studies. Pluronic organogel containing Pregabalin and diclofenac diethylamine with oleic acid was fabricated. Duro-Tak® (87-2196) was added to the organogel formulation as a pressure-sensitive adhesive to sustain the release profile of these two therapeutic molecules. The adhesive organogel was characterized for particle size, scanning electron microscopy, and contact angle measurement. The HPLC method developed for the quantification of the dual drug showed a retention time of 3.84 minutes and 9.69 minutes for pregabalin and diclofenac, respectively. The fabricated nanogel adhesive formulation showed the desired results with particle size and contact angle of 282 ± 57 nm and ≥120⁰, respectively. In vitro studies showed the percentage cumulative release of 24.90 ± 4.65% and 33.29 ± 4.81% for pregabalin and diclofenac, respectively. In order to accomplish transdermal permeation, the suggested hypothesis of fabricating PG and DEE nano-organogel in combination with permeation enhancers will be a viable drug delivery method. In comparison to a traditional gel formulation, oleic acid as a permeation enhancer increased the penetration of both PG and DEE from the organogel formulation. Notably, the studies showed that the use of pressure-sensitive adhesives enabled the sustained release of both PG and DEE.Therefore, the results anticipated the hypothesis that the transdermal delivery of adhesive PG and DEE-based nanogel across the human skin can be achieved to inhibit inflammation and pain.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-04DOI: 10.2174/0115665240309647240516042716
Mina Afrashteh, Mohammad Rahmati-Yamchi, Mohammad Shimia, Bahman Yousefi, Maryam Majidinia
Glioblastoma multiforme [GBM] is a highly aggressive grade IV central nervous system tumor with a dismal prognosis. Factors such as late detection, treatment limitations due to its aggressive nature, and, notably, drug resistance significantly affect clinical outcomes. Despite the effectiveness of Temozolomide [TMZ], a potent chemotherapy agent, the development of drug resistance remains a major challenge. Given the poor survival rates and chemoresistance, there is an urgent need for novel treatment strategies. Non-coding RNAs, particularly microRNAs [miRNAs], offer a promising approach to GBM diagnosis and treatment. These small non-coding RNAs play crucial roles in tumor progression, either suppressing or promoting oncogenic characteristics. The phosphoinositide-3 kinase [PI3K]/AKT/ mTOR pathway, which regulates essential biological processes like proliferation and survival, is a key target of miRNAs in cancer. Studies have underscored the significance of PI3K/AKT/mTOR signaling in drug resistance development and its interplay with non-coding RNAs as mediators of tumorigenesis. This review aims to outline the involvement of PI3K/AKT/mTOR signaling in miRNA modulation and strategies to overcome chemoresistance in GBM.
{"title":"Emerging Insights into the PI3K/AKT/mTOR Signaling Pathway and Non-Coding RNA-mediated Drug Resistance in Glioblastoma.","authors":"Mina Afrashteh, Mohammad Rahmati-Yamchi, Mohammad Shimia, Bahman Yousefi, Maryam Majidinia","doi":"10.2174/0115665240309647240516042716","DOIUrl":"https://doi.org/10.2174/0115665240309647240516042716","url":null,"abstract":"<p><p>Glioblastoma multiforme [GBM] is a highly aggressive grade IV central nervous system tumor with a dismal prognosis. Factors such as late detection, treatment limitations due to its aggressive nature, and, notably, drug resistance significantly affect clinical outcomes. Despite the effectiveness of Temozolomide [TMZ], a potent chemotherapy agent, the development of drug resistance remains a major challenge. Given the poor survival rates and chemoresistance, there is an urgent need for novel treatment strategies. Non-coding RNAs, particularly microRNAs [miRNAs], offer a promising approach to GBM diagnosis and treatment. These small non-coding RNAs play crucial roles in tumor progression, either suppressing or promoting oncogenic characteristics. The phosphoinositide-3 kinase [PI3K]/AKT/ mTOR pathway, which regulates essential biological processes like proliferation and survival, is a key target of miRNAs in cancer. Studies have underscored the significance of PI3K/AKT/mTOR signaling in drug resistance development and its interplay with non-coding RNAs as mediators of tumorigenesis. This review aims to outline the involvement of PI3K/AKT/mTOR signaling in miRNA modulation and strategies to overcome chemoresistance in GBM.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-03DOI: 10.2174/0115665240304363240524103203
Yun You, Guoliang Wang, Qi Cui, Xiangfu Sun, Li Wan, Quanchao Sun
Introduction: The major complication of Obliterative Bronchiolitis (OB) is characterized by epithelial cell loss, fibrosis, and luminal occlusion of the terminal small airways, which limits the long-term survival of the recipient after lung transplantation. However, the underlying mechanisms are still not fully clarified. This research aims to investigate whether iron overload-induced ferroptosis is involved in OB development and provide a new target for OB prevention.
Materials and methods: Allograft orthotopic tracheal transplantation in mice was applied in our study. Ferrostatin-1 and deferoxamine were administrated to inhibit ferroptosis and get rid of ferric iron, while iron dextran was used to induce an iron overload condition in the recipient. The histological examination, luminal occlusion rate, collagen deposition, iron level, ferroptosis marker (GPX4, PTGS2), and mitochondrial morphological changes of the graft were evaluated in mice.
Results: Our research indicated that ferroptosis and iron overload contribute to OB development, while ferroptosis inhibition and iron chelator could reverse the changes. Iron overload exacerbated OB development after orthotopic tracheal transplantation via promoting ferroptosis.
Conclusion: Overall, this research demonstrated that iron overload-induced ferroptosis is involved in OB, which may be a potential therapeutic target for OB after lung transplantation.
导言:闭塞性支气管炎(OB)的主要并发症是上皮细胞脱落、纤维化和末端小气道管腔闭塞,这限制了肺移植受者的长期生存。然而,其潜在机制仍未完全阐明。本研究旨在探讨铁超载诱导的铁蛋白沉积是否参与了OB的发生,并为OB的预防提供新的靶点:材料和方法:本研究采用同种异体气管移植小鼠。材料:我们的研究采用了异体气管正位移植小鼠,给予铁前列素-1和去铁胺抑制铁变态反应并清除铁,同时使用右旋糖酐铁诱导受体铁超载。对小鼠移植物的组织学检查、管腔闭塞率、胶原沉积、铁含量、铁变态反应标记物(GPX4、PTGS2)和线粒体形态变化进行了评估:结果:我们的研究表明,铁变态反应和铁超载会导致 OB 的发生,而抑制铁变态反应和铁螯合剂能逆转这种变化。铁超载通过促进铁变态反应加剧了气管移植后OB的发展:总之,本研究证明铁超载诱导的铁嗜酸参与了OB的发生,这可能是肺移植后OB的潜在治疗靶点。
{"title":"Iron Overload-induced Ferroptosis as a Target for Protection against Obliterative Bronchiolitis after Orthotopic Tracheal Transplantation in Mice.","authors":"Yun You, Guoliang Wang, Qi Cui, Xiangfu Sun, Li Wan, Quanchao Sun","doi":"10.2174/0115665240304363240524103203","DOIUrl":"https://doi.org/10.2174/0115665240304363240524103203","url":null,"abstract":"<p><strong>Introduction: </strong>The major complication of Obliterative Bronchiolitis (OB) is characterized by epithelial cell loss, fibrosis, and luminal occlusion of the terminal small airways, which limits the long-term survival of the recipient after lung transplantation. However, the underlying mechanisms are still not fully clarified. This research aims to investigate whether iron overload-induced ferroptosis is involved in OB development and provide a new target for OB prevention.</p><p><strong>Materials and methods: </strong>Allograft orthotopic tracheal transplantation in mice was applied in our study. Ferrostatin-1 and deferoxamine were administrated to inhibit ferroptosis and get rid of ferric iron, while iron dextran was used to induce an iron overload condition in the recipient. The histological examination, luminal occlusion rate, collagen deposition, iron level, ferroptosis marker (GPX4, PTGS2), and mitochondrial morphological changes of the graft were evaluated in mice.</p><p><strong>Results: </strong>Our research indicated that ferroptosis and iron overload contribute to OB development, while ferroptosis inhibition and iron chelator could reverse the changes. Iron overload exacerbated OB development after orthotopic tracheal transplantation via promoting ferroptosis.</p><p><strong>Conclusion: </strong>Overall, this research demonstrated that iron overload-induced ferroptosis is involved in OB, which may be a potential therapeutic target for OB after lung transplantation.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-27DOI: 10.2174/0115665240290075240514164601
Roghayeh Tofigh, Reza Safaralizadeh, Mohammadali Hosseinpourfeizi, Nima Hemmat, Behzad Baradaran
miRNA-21 is regarded as both an abundant and highly conserved member of the microRNA (miRNA) family. It is expressed in virtually every cell and is responsible for critical regulatory actions that are important in health and disease. This microRNA has been shown to potentially have a role in the pathogenesis of several immune-related disorders, including autoimmune diseases, such as Multiple sclerosis and systemic lupus erythematosus, as two prominent examples of diseases that might be involved. In the current research, we looked at the role of miRNA-21, regarded as one of the most significant pathogenic miRNAs with a role in the development of autoimmune illness.
{"title":"miRNA-21, an Important Regulator of Autoimmune Diseases.","authors":"Roghayeh Tofigh, Reza Safaralizadeh, Mohammadali Hosseinpourfeizi, Nima Hemmat, Behzad Baradaran","doi":"10.2174/0115665240290075240514164601","DOIUrl":"https://doi.org/10.2174/0115665240290075240514164601","url":null,"abstract":"<p><p>miRNA-21 is regarded as both an abundant and highly conserved member of the microRNA (miRNA) family. It is expressed in virtually every cell and is responsible for critical regulatory actions that are important in health and disease. This microRNA has been shown to potentially have a role in the pathogenesis of several immune-related disorders, including autoimmune diseases, such as Multiple sclerosis and systemic lupus erythematosus, as two prominent examples of diseases that might be involved. In the current research, we looked at the role of miRNA-21, regarded as one of the most significant pathogenic miRNAs with a role in the development of autoimmune illness.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The human leukocyte antigen (HLA, also known as the major histocompatibility complex or MHC) system, is responsible for immune monitoring of the intracellular proteome of all nucleated cells. The presentation of antigen peptides separates malignant or infected cells from their healthy counterparts and forms aberrant cells tagged as the foundation for identification. Therefore, peptide-MHC molecules can give potential diagnostic targets for cancer or infection. TCR-like antibodies recognize specific peptides that bind to MHC molecules, allowing them to target Such inaccessible cytoplasmic or nuclear tumors or virus-associated antigens. It binds to MHC, presenting peptides found on the surface of target cells. These antibodies have shown promising clinical applications in diagnosing and imaging cancer and infected cells. This review presents the current situation of TCR-like antibodies and its prospects for application in the field of intracellular antigen diagnostics. It also lists the potential application targets of TCR, like antibodies in various disease diagnoses, providing valuable information for developing diagnostic reagents and selecting targets in the future.
{"title":"The Future of TCR-like Antibodies in Diagnosis and Potential Application Targets.","authors":"Huaqiang Liu, Sylvia Annabel Dass, Venugopal Balakrishnan, Fazlina Nordin, Gee Jun Tye","doi":"10.2174/0115665240297179240514030532","DOIUrl":"https://doi.org/10.2174/0115665240297179240514030532","url":null,"abstract":"<p><p>The human leukocyte antigen (HLA, also known as the major histocompatibility complex or MHC) system, is responsible for immune monitoring of the intracellular proteome of all nucleated cells. The presentation of antigen peptides separates malignant or infected cells from their healthy counterparts and forms aberrant cells tagged as the foundation for identification. Therefore, peptide-MHC molecules can give potential diagnostic targets for cancer or infection. TCR-like antibodies recognize specific peptides that bind to MHC molecules, allowing them to target Such inaccessible cytoplasmic or nuclear tumors or virus-associated antigens. It binds to MHC, presenting peptides found on the surface of target cells. These antibodies have shown promising clinical applications in diagnosing and imaging cancer and infected cells. This review presents the current situation of TCR-like antibodies and its prospects for application in the field of intracellular antigen diagnostics. It also lists the potential application targets of TCR, like antibodies in various disease diagnoses, providing valuable information for developing diagnostic reagents and selecting targets in the future.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-22DOI: 10.2174/0115665240298173240427042624
Shijie Wu, Kun Wu, Yuqing Yang, Zhiwen Ou, Xiaoyong Lei, Xiaoyan Yang
As lncRNAs have increasingly been investigated, they are no longer simply defined as RNAs with no transcription capability. Studies have identified significant associations between the abnormal expression of lncRNAs and human diseases, particularly the mechanisms by which lncRNAs play a part in cancers, which are of considerable attention to researchers. As a result of the complex spatial structure, the mechanisms of interaction of lncRNAs in cancer cells are also complicated and diversified. Among a series of lncRNAs, TUG1, which is now considered to be a very high-value lncRNA, has recently been identified to express abnormally in some malignancies, leading to different alterations in cancer cells proliferation, migration, invasion, apoptosis, and drug resistance, and hence promoting or inhibiting cancer progression. Current studies have implicitly indicated that TUG1 can be used as a therapeutic target for human cancers. However, the biological functions of TUG1 have been studied for a short period of time, and the complete molecular mechanism still needs to be clarified. Accordingly, this review focuses on the principal molecular mechanisms of TUG1 in human cancers and the specific mechanisms of action in different cancer development processes based on existing studies.
{"title":"LncRNA TUG1 and its Molecular Mechanisms in Human Cancer.","authors":"Shijie Wu, Kun Wu, Yuqing Yang, Zhiwen Ou, Xiaoyong Lei, Xiaoyan Yang","doi":"10.2174/0115665240298173240427042624","DOIUrl":"https://doi.org/10.2174/0115665240298173240427042624","url":null,"abstract":"<p><p>As lncRNAs have increasingly been investigated, they are no longer simply defined as RNAs with no transcription capability. Studies have identified significant associations between the abnormal expression of lncRNAs and human diseases, particularly the mechanisms by which lncRNAs play a part in cancers, which are of considerable attention to researchers. As a result of the complex spatial structure, the mechanisms of interaction of lncRNAs in cancer cells are also complicated and diversified. Among a series of lncRNAs, TUG1, which is now considered to be a very high-value lncRNA, has recently been identified to express abnormally in some malignancies, leading to different alterations in cancer cells proliferation, migration, invasion, apoptosis, and drug resistance, and hence promoting or inhibiting cancer progression. Current studies have implicitly indicated that TUG1 can be used as a therapeutic target for human cancers. However, the biological functions of TUG1 have been studied for a short period of time, and the complete molecular mechanism still needs to be clarified. Accordingly, this review focuses on the principal molecular mechanisms of TUG1 in human cancers and the specific mechanisms of action in different cancer development processes based on existing studies.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-21DOI: 10.2174/0115665240292079240513093708
Hong Zhou, Yuqing Xia, Rui Zhu, Yuemei Zhang, Xinming Zhang, Yongjian Zhang, Jun Wang
Ribosomal DNA (rDNA) is important in the nucleolus and nuclear organization of human cells. Defective rDNA repeat maintenance has been reported to be closely associated with neurological disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, depression, suicide, etc. However, there has not been a comprehensive review on the role of rDNA in these disorders. In this review, we have summarized the role of rDNA in major neurological disorders to sort out the correlation between rDNA and neurological diseases and provided insights for therapy with rDNA as a target.
{"title":"Ribosomal DNA and Neurological Disorders.","authors":"Hong Zhou, Yuqing Xia, Rui Zhu, Yuemei Zhang, Xinming Zhang, Yongjian Zhang, Jun Wang","doi":"10.2174/0115665240292079240513093708","DOIUrl":"https://doi.org/10.2174/0115665240292079240513093708","url":null,"abstract":"<p><p>Ribosomal DNA (rDNA) is important in the nucleolus and nuclear organization of human cells. Defective rDNA repeat maintenance has been reported to be closely associated with neurological disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, depression, suicide, etc. However, there has not been a comprehensive review on the role of rDNA in these disorders. In this review, we have summarized the role of rDNA in major neurological disorders to sort out the correlation between rDNA and neurological diseases and provided insights for therapy with rDNA as a target.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-17DOI: 10.2174/0115665240303179240427071748
Suman Kumar Ray, Sukhes Mukherjee
Hypoxia, characterized by insufficient oxygen supply to tissues, is a significant factor in tumor growth and resistance to treatment. The hypoxia-inducible factor (HIF) signaling pathway is activated when oxygen levels decline, influencing cell activities and promoting tumor progression. HIF-1α and HIF-2α are the main targets for therapeutic intervention in tumors. Nevertheless, the significance of HIF-2α is often overlooked. This review examines the physiological role of HIF-2α in tumor growth and its involvement in tumor growth. HIFs, composed of hypoxia-responsive α and oxygeninsensitive β subunits, play a crucial role in controlling gene expression in both normal and solid tumor tissues under low oxygen levels. HIF-3α, formerly considered a detrimental modulator of HIF-regulated genes, exerts a transcriptional regulatory role by inhibiting gene expression through competition with HIF-1α and HIF-2α for binding to transcriptional sites in target genes under hypoxia. Recent research indicates that various HIF-3 variants exhibit distinct and potentially contrasting functionalities. Hypoxia often occurs during the initiation and progression of cancer formation. Recent research has discovered that HIF-2α, also known as endothelial PAS domain protein 1, has a significant impact on tumors. HIF-2α is a significant cancer-causing gene and a crucial predictor of prognosis in non-small cell lung cancer. However, due to limited research investigating the relationship between HIF-2α and small-cell lung cancer, it is not possible to reach a definitive conclusion. HIF-2α plays a vital function in cancer by preserving the stemness of cancer cells. This review provides a comprehensive overview of HIF-2 and the role of HIF-3 in various cancer-related processes, as well as its potential as a targeted therapeutic approach.
{"title":"Limning of HIF-2 and HIF-3 in the Tumor Microenvironment: Developing Concepts for the Treatment of Hypoxic Cancer.","authors":"Suman Kumar Ray, Sukhes Mukherjee","doi":"10.2174/0115665240303179240427071748","DOIUrl":"https://doi.org/10.2174/0115665240303179240427071748","url":null,"abstract":"<p><p>Hypoxia, characterized by insufficient oxygen supply to tissues, is a significant factor in tumor growth and resistance to treatment. The hypoxia-inducible factor (HIF) signaling pathway is activated when oxygen levels decline, influencing cell activities and promoting tumor progression. HIF-1α and HIF-2α are the main targets for therapeutic intervention in tumors. Nevertheless, the significance of HIF-2α is often overlooked. This review examines the physiological role of HIF-2α in tumor growth and its involvement in tumor growth. HIFs, composed of hypoxia-responsive α and oxygeninsensitive β subunits, play a crucial role in controlling gene expression in both normal and solid tumor tissues under low oxygen levels. HIF-3α, formerly considered a detrimental modulator of HIF-regulated genes, exerts a transcriptional regulatory role by inhibiting gene expression through competition with HIF-1α and HIF-2α for binding to transcriptional sites in target genes under hypoxia. Recent research indicates that various HIF-3 variants exhibit distinct and potentially contrasting functionalities. Hypoxia often occurs during the initiation and progression of cancer formation. Recent research has discovered that HIF-2α, also known as endothelial PAS domain protein 1, has a significant impact on tumors. HIF-2α is a significant cancer-causing gene and a crucial predictor of prognosis in non-small cell lung cancer. However, due to limited research investigating the relationship between HIF-2α and small-cell lung cancer, it is not possible to reach a definitive conclusion. HIF-2α plays a vital function in cancer by preserving the stemness of cancer cells. This review provides a comprehensive overview of HIF-2 and the role of HIF-3 in various cancer-related processes, as well as its potential as a targeted therapeutic approach.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.2174/0115665240294605240426123650
Xiaoting Yangzhong, Shu Hua, Yiqiong Wen, Xiaoqing Bi, Min Li, Yuanyuan Zheng, Shibo Sun
Obstructive sleep apnea [OSA] is widespread in the population and affects as many as one billion people worldwide. OSA is associated with dysfunction of the brain system that controls breathing, which leads to intermittent hypoxia [IH], hypercapnia, and oxidative stress [OS]. The number of NOD-like receptor family pyrin domain-containing [NLRP3] inflammasome was increased after IH, hypercapnia, and OS. NLRP3 inflammasome is closely related to inflammation. NLRP3 inflammasome causes a series of inflammatory diseases by activating IL-1β and IL-18. Subsequently, NLRP3 inflammasome plays an important role in the complications of OSA, including Type 2 diabetes [T2DM], coronary heart disease [CHD], hypertension, neuroinflammation, and depression. This review will introduce the basic composition and structure of the NLRP3 inflammasome and focus on the relationship between the NLRP3 inflammasome and OSA and OSA complications. We can deeply understand how NLRP3 inflammasome is strongly associated with OSA and OSA complications.
阻塞性睡眠呼吸暂停[OSA]在人群中非常普遍,影响着全球多达十亿人。OSA 与控制呼吸的大脑系统功能失调有关,导致间歇性缺氧 [IH]、高碳酸血症和氧化应激 [OS]。IH、高碳酸血症和 OS 后,含 NOD 样受体家族 pyrin 结构域的 [NLRP3] 炎性体数量增加。NLRP3 炎症小体与炎症密切相关。NLRP3 炎性体通过激活 IL-1β 和 IL-18 引发一系列炎症性疾病。随后,NLRP3 炎性体在 OSA 的并发症中扮演了重要角色,包括 2 型糖尿病(T2DM)、冠心病(CHD)、高血压、神经炎症和抑郁症。本综述将介绍 NLRP3 炎性体的基本组成和结构,并重点讨论 NLRP3 炎性体与 OSA 及 OSA 并发症之间的关系。我们可以深入了解NLRP3炎症小体与OSA及OSA并发症的密切关系。
{"title":"NLRP3 Inflammasome Triggers Inflammation of Obstructive Sleep Apnea.","authors":"Xiaoting Yangzhong, Shu Hua, Yiqiong Wen, Xiaoqing Bi, Min Li, Yuanyuan Zheng, Shibo Sun","doi":"10.2174/0115665240294605240426123650","DOIUrl":"https://doi.org/10.2174/0115665240294605240426123650","url":null,"abstract":"<p><p>Obstructive sleep apnea [OSA] is widespread in the population and affects as many as one billion people worldwide. OSA is associated with dysfunction of the brain system that controls breathing, which leads to intermittent hypoxia [IH], hypercapnia, and oxidative stress [OS]. The number of NOD-like receptor family pyrin domain-containing [NLRP3] inflammasome was increased after IH, hypercapnia, and OS. NLRP3 inflammasome is closely related to inflammation. NLRP3 inflammasome causes a series of inflammatory diseases by activating IL-1β and IL-18. Subsequently, NLRP3 inflammasome plays an important role in the complications of OSA, including Type 2 diabetes [T2DM], coronary heart disease [CHD], hypertension, neuroinflammation, and depression. This review will introduce the basic composition and structure of the NLRP3 inflammasome and focus on the relationship between the NLRP3 inflammasome and OSA and OSA complications. We can deeply understand how NLRP3 inflammasome is strongly associated with OSA and OSA complications.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.2174/0115665240290237240424054233
Jinyu Hu, Qinxuan Xu, Yuchang Fei, Zhengwei Tan, Lei Pan
Background: Gastric Cancer (GC) has become one of the most important causes of cancer-related deaths worldwide due to its intractability. Studying the mechanisms of gastric carcinogenesis, recurrence, and metastasis, and searching for new therapeutic targets have become the main directions of today's gastric cancer research. Lactate is considered a metabolic by-product of tumor aerobic glycolysis, which can regulate tumor development through various mechanisms, including cell cycle regulation, immunosuppression, and energy metabolism. However, the effects of genes related to lactate metabolism on the prognosis and tumor microenvironmental characteristics of GC patients are unknown.
Method: In this study, we have collected gene expression data of gastric cancer from The Cancer Genome Atlas (TCGA) and identified differentially expressed genes in gastric cancer using the "Limma" software package.
Result: 76 differentially expressed lactate metabolism-related genes were screened, and then the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analysis were employed that identified 8 genes, constructed Lactate Metabolism-related gene signals (LMRs), and verified the reliability of the prognostic risk mapping by using TCGA training set and TCGA internal test set. Finally, the functional enrichment analysis was employed to identify the molecular mechanism.
Conclusion: Eight lactate metabolism-related genes were constructed into a new predictive signal that better predicted the overall survival of gastric cancer patients and can guide clinical decisions for more precise and personalized treatment.
{"title":"Establishment and Validation of Lactate Metabolism-Related Genes as a Prognostic Model for Gastric Cancer.","authors":"Jinyu Hu, Qinxuan Xu, Yuchang Fei, Zhengwei Tan, Lei Pan","doi":"10.2174/0115665240290237240424054233","DOIUrl":"https://doi.org/10.2174/0115665240290237240424054233","url":null,"abstract":"<p><strong>Background: </strong>Gastric Cancer (GC) has become one of the most important causes of cancer-related deaths worldwide due to its intractability. Studying the mechanisms of gastric carcinogenesis, recurrence, and metastasis, and searching for new therapeutic targets have become the main directions of today's gastric cancer research. Lactate is considered a metabolic by-product of tumor aerobic glycolysis, which can regulate tumor development through various mechanisms, including cell cycle regulation, immunosuppression, and energy metabolism. However, the effects of genes related to lactate metabolism on the prognosis and tumor microenvironmental characteristics of GC patients are unknown. <P> </P> Method: In this study, we have collected gene expression data of gastric cancer from The Cancer Genome Atlas (TCGA) and identified differentially expressed genes in gastric cancer using the \"Limma\" software package. <P> </P> Result: 76 differentially expressed lactate metabolism-related genes were screened, and then the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analysis were employed that identified 8 genes, constructed Lactate Metabolism-related gene signals (LMRs), and verified the reliability of the prognostic risk mapping by using TCGA training set and TCGA internal test set. Finally, the functional enrichment analysis was employed to identify the molecular mechanism. <P> </P> Conclusion: Eight lactate metabolism-related genes were constructed into a new predictive signal that better predicted the overall survival of gastric cancer patients and can guide clinical decisions for more precise and personalized treatment.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}