Pub Date : 2024-05-01DOI: 10.4062/biomolther.2024.004
Hae Ran Lee, Seong-Min Hong, Kyohee Cho, Seon Hyeok Kim, Eunji Ko, Eunyoo Lee, Hyun Jin Kim, Se Yeong Jeon, Seon Gil Do, Sun Yeou Kim
{"title":"Erratum to \"Potential Role of Dietary Salmon Nasal Cartilage Proteoglycan on UVB-Induced Photoaged Skin\" [Biomol. Ther. 32 (2024) 249-260].","authors":"Hae Ran Lee, Seong-Min Hong, Kyohee Cho, Seon Hyeok Kim, Eunji Ko, Eunyoo Lee, Hyun Jin Kim, Se Yeong Jeon, Seon Gil Do, Sun Yeou Kim","doi":"10.4062/biomolther.2024.004","DOIUrl":"https://doi.org/10.4062/biomolther.2024.004","url":null,"abstract":"","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 3","pages":"399"},"PeriodicalIF":3.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11063478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861980","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 : 2024-04-17DOI: 10.4062/biomolther.2024.052
Supriya Tiwari, Nikita Basnet, Ji Woong Choi
Lysophosphatidic acid receptor 1 (LPA1) plays a critical role in brain injury following a transient brain ischemic stroke. However, its role in permanent brain ischemic stroke remains unknown. To address this, we investigated whether LPA1 could contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO). A selective LPA1 antagonist (AM152) was used as a pharmacological tool for this investigation. When AM152 was given to pMCAO-challenged mice one hour after occlusion, pMCAO-induced brain damage such as brain infarction, functional neurological deficits, apoptosis, and blood-brain barrier disruption was significantly attenuated. Histological analyses demonstrated that AM152 administration attenuated microglial activation and proliferation in injured brain after pMCAO challenge. AM152 administration also attenuated abnormal neuroinflammatory responses by decreasing expression levels of pro-inflammatory cytokines while increasing expression levels of anti-inflammatory cytokines in the injured brain. As underlying effector pathways, NF-κB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in LPA1-dependent pathogenesis. Collectively, these results demonstrate that LPA1 can contribute to brain injury by permanent ischemic stroke, along with relevant pathogenic events in an injured brain.
{"title":"Lysophosphatidic Acid Receptor 1 Plays a Pathogenic Role in Permanent Brain Ischemic Stroke by Modulating Neuroinflammatory Responses.","authors":"Supriya Tiwari, Nikita Basnet, Ji Woong Choi","doi":"10.4062/biomolther.2024.052","DOIUrl":"https://doi.org/10.4062/biomolther.2024.052","url":null,"abstract":"Lysophosphatidic acid receptor 1 (LPA<sub>1</sub>) plays a critical role in brain injury following a transient brain ischemic stroke. However, its role in permanent brain ischemic stroke remains unknown. To address this, we investigated whether LPA<sub>1</sub> could contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO). A selective LPA<sub>1</sub> antagonist (AM152) was used as a pharmacological tool for this investigation. When AM152 was given to pMCAO-challenged mice one hour after occlusion, pMCAO-induced brain damage such as brain infarction, functional neurological deficits, apoptosis, and blood-brain barrier disruption was significantly attenuated. Histological analyses demonstrated that AM152 administration attenuated microglial activation and proliferation in injured brain after pMCAO challenge. AM152 administration also attenuated abnormal neuroinflammatory responses by decreasing expression levels of pro-inflammatory cytokines while increasing expression levels of anti-inflammatory cytokines in the injured brain. As underlying effector pathways, NF-κB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in LPA<sub>1</sub>-dependent pathogenesis. Collectively, these results demonstrate that LPA<sub>1</sub> can contribute to brain injury by permanent ischemic stroke, along with relevant pathogenic events in an injured brain.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"184 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613610","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 : 2024-04-11DOI: 10.4062/biomolther.2024.012
Hyun Hwangbo, Cheol Park, EunJin Bang, Hyuk Soon Kim, Sung-Jin Bae, Eunjeong Kim, Youngmi Jung, Sun-Hee Leem, Young Rok Seo, Su Hyun Hong, Gi-Young Kim, Jin Won Hyun, Yung Hyun Choi
Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H2O2) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H2O2-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H2O2-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H2O2-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H2O2-mediated calcium (Ca2+) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca2+-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca2+-mediated ER stress by minimizing oxidative stress, thereby inhibiting H2O2-induced cytotoxicity in C2C12 myoblasts.
氧化应激会导致包括肌肉在内的各种器官发生慢性疾病。据报道，山茱萸中所含的一种鸢尾甙作为一种天然化合物，具有预防各种疾病的优势。然而，关于这种植物化学物质是否对肌肉细胞的氧化应激有抑制作用，目前还没有很好的报道。因此，本研究旨在评估吗菌腈是否能保护小鼠 C2C12 肌细胞免受过氧化氢（H2O2）诱导的氧化损伤。我们的研究结果表明，吗菌腈预处理能够抑制细胞毒性，同时抑制 H2O2 诱导的 DNA 损伤和细胞凋亡。莫罗尼苷还通过阻断细胞活性氧和线粒体超氧化物的产生以及增加谷胱甘肽的产生，明显提高了H2O2诱导的C2C12细胞的抗氧化能力。此外，莫罗尼苷还能有效减轻 H2O2 诱导的线粒体损伤和内质网（ER）应激，抑制细胞质中细胞色素 c 的泄漏和 ER 应激相关蛋白的表达。此外，吗菌灵还能中和 H2O2 介导的线粒体钙（Ca2+）超载，并减轻钙蛋白酶（依赖于细胞膜 Ca2+ 的蛋白酶）的表达。总之，这些研究结果表明，吗菌腈通过减少氧化应激来防止线粒体损伤和 Ca2+ 介导的 ER 应激，从而抑制了 H2O2- 在 C2C12 肌细胞中诱导的细胞毒性。
{"title":"Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress.","authors":"Hyun Hwangbo, Cheol Park, EunJin Bang, Hyuk Soon Kim, Sung-Jin Bae, Eunjeong Kim, Youngmi Jung, Sun-Hee Leem, Young Rok Seo, Su Hyun Hong, Gi-Young Kim, Jin Won Hyun, Yung Hyun Choi","doi":"10.4062/biomolther.2024.012","DOIUrl":"https://doi.org/10.4062/biomolther.2024.012","url":null,"abstract":"Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in <i>Cornus officinalis</i>, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H<sub>2</sub>O<sub>2</sub>-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H<sub>2</sub>O<sub>2</sub>-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H<sub>2</sub>O<sub>2</sub>-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H<sub>2</sub>O<sub>2</sub>-mediated calcium (Ca<sup>2+</sup>) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca<sup>2+</sup>-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca<sup>2+</sup>-mediated ER stress by minimizing oxidative stress, thereby inhibiting H<sub>2</sub>O<sub>2</sub>-induced cytotoxicity in C2C12 myoblasts.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"55 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602951","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}
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.
{"title":"Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma.","authors":"Dae Ui Lee, Beom Seok Han, Kyung Hee Jung, Soon-Sun Hong","doi":"10.4062/biomolther.2024.029","DOIUrl":"https://doi.org/10.4062/biomolther.2024.029","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"27 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570195","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 : 2024-04-09DOI: 10.4062/biomolther.2023.207
Yejin Ahn, Jong Hoon Park
Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.
{"title":"Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis.","authors":"Yejin Ahn, Jong Hoon Park","doi":"10.4062/biomolther.2023.207","DOIUrl":"https://doi.org/10.4062/biomolther.2023.207","url":null,"abstract":"Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"37 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570202","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 : 2024-04-09DOI: 10.4062/biomolther.2023.159
Seo-Yeon Choi, Suin Kim, Ji-Young Jeon, Min-Gul Kim, Sun-Young Lee, Kwang-Hee Shin
This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q ExactiveTM Focus Hybrid Quadrupole-OrbitrapTM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 μm) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40°C. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.
{"title":"Metabolomic Profiles in Patients with Cervical Cancer Undergoing Cisplatin and Radiation Therapy.","authors":"Seo-Yeon Choi, Suin Kim, Ji-Young Jeon, Min-Gul Kim, Sun-Young Lee, Kwang-Hee Shin","doi":"10.4062/biomolther.2023.159","DOIUrl":"https://doi.org/10.4062/biomolther.2023.159","url":null,"abstract":"This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q Exactive<sup>TM</sup> Focus Hybrid Quadrupole-Orbitrap<sup>TM</sup> mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 μm) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40°C. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"202 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570213","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 : 2024-04-09DOI: 10.4062/biomolther.2023.184
Yongun Park, Yunn Me Me Paing, Namki Cho, Changyoun Kim, Jiho Yoo, Ji Woong Choi, Sung Hoon Lee
Compared to other organs, the brain has limited antioxidant defenses. In particular, the hippocampus is the central region for learning and memory and is highly susceptible to oxidative stress. Glial cells are the most abundant cells in the brain, and sustained glial cell activation is critical to the neuroinflammation that aggravates neuropathology and neurotoxicity. Therefore, regulating glial cell activation is a promising neurotherapeutic treatment. Quinic acid and its derivatives possess anti-oxidant and anti-inflammatory properties. Although previous studies have evidenced quinic acid's benefit on the brain, in vivo and in vitro analyses of its anti-oxidant and anti-inflammatory properties in glial cells have yet to be established. This study investigated quinic acid's rescue effect in lipopolysaccharide (LPS)-induced behavior impairment. Orally administering quinic acid restored social impairment and LPS-induced spatial and fear memory. In addition, quinic acid inhibited proinflammatory mediator, oxidative stress marker, and mitogen-activated protein kinase (MAPK) activation in the LPS-injected hippocampus. Quinic acid inhibited nitrite release and extracellular signal-regulated kinase (ERK) phosphorylation in LPS-stimulated astrocytes. Collectively, quinic acid restored impaired neuroinflammation-induced behavior by regulating proinflammatory mediator and ERK activation in astrocytes, demonstrating its potential as a therapeutic agent for neuroinflammation-induced brain disease treatments.
{"title":"Quinic Acid Alleviates Behavior Impairment by Reducing Neuroinflammation and MAPK Activation in LPS-Treated Mice.","authors":"Yongun Park, Yunn Me Me Paing, Namki Cho, Changyoun Kim, Jiho Yoo, Ji Woong Choi, Sung Hoon Lee","doi":"10.4062/biomolther.2023.184","DOIUrl":"https://doi.org/10.4062/biomolther.2023.184","url":null,"abstract":"Compared to other organs, the brain has limited antioxidant defenses. In particular, the hippocampus is the central region for learning and memory and is highly susceptible to oxidative stress. Glial cells are the most abundant cells in the brain, and sustained glial cell activation is critical to the neuroinflammation that aggravates neuropathology and neurotoxicity. Therefore, regulating glial cell activation is a promising neurotherapeutic treatment. Quinic acid and its derivatives possess anti-oxidant and anti-inflammatory properties. Although previous studies have evidenced quinic acid's benefit on the brain, <i>in vivo</i> and <i>in vitro</i> analyses of its anti-oxidant and anti-inflammatory properties in glial cells have yet to be established. This study investigated quinic acid's rescue effect in lipopolysaccharide (LPS)-induced behavior impairment. Orally administering quinic acid restored social impairment and LPS-induced spatial and fear memory. In addition, quinic acid inhibited proinflammatory mediator, oxidative stress marker, and mitogen-activated protein kinase (MAPK) activation in the LPS-injected hippocampus. Quinic acid inhibited nitrite release and extracellular signal-regulated kinase (ERK) phosphorylation in LPS-stimulated astrocytes. Collectively, quinic acid restored impaired neuroinflammation-induced behavior by regulating proinflammatory mediator and ERK activation in astrocytes, demonstrating its potential as a therapeutic agent for neuroinflammation-induced brain disease treatments.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"57 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570193","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 : 2024-04-09DOI: 10.4062/biomolther.2023.186
Hyuk-Jun Yoon, Heui Woong Moon, Young Sil Min, Fanxue Jin, Joon Seok Bang, Uy Dong Sohn, Hyun Dong Je
In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.
{"title":"Effect of Kaempferol on Modulation of Vascular Contractility Mainly through PKC and CPI-17 Inactivation.","authors":"Hyuk-Jun Yoon, Heui Woong Moon, Young Sil Min, Fanxue Jin, Joon Seok Bang, Uy Dong Sohn, Hyun Dong Je","doi":"10.4062/biomolther.2023.186","DOIUrl":"https://doi.org/10.4062/biomolther.2023.186","url":null,"abstract":"In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"29 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570384","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}
Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44highCD133high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.
虫草素是从冬虫夏草中分离出来的一种珍贵的生物活性成分，据报道它具有抗癌潜力，并能增强化疗药物对各种癌症的效果。然而，虫草素能使胆管癌（CCA）细胞对吉西他滨化疗敏感的能力尚未得到评估。目前的研究就是为了评估上述情况及其相关机制。研究分析了虫草素与吉西他滨联用对 CCA SNU478 细胞株癌干样特性的影响，包括其抗凋亡、迁移和抗氧化作用。此外，还在 CCA 异种移植模型中评估了虫草素与吉西他滨的联合治疗效果。虫草素能明显降低SNU478细胞的存活率，与吉西他滨联用时还能额外降低细胞的存活率。虫草素和吉西他滨联合治疗可显著增加Annexin V+细胞群，并下调B细胞淋巴瘤2（Bcl-2）的表达，这表明虫草素+吉西他滨组细胞活力的降低可能是由于凋亡增加所致。此外，在伤口愈合和跨孔迁移试验中，虫草素和吉西他滨联合治疗显著降低了SNU478细胞的迁移能力。研究发现，虫草素和吉西他滨联合治疗可降低SNU478细胞中的CD44highCD133high群体和性别决定区Y-box 2（Sox-2）的表达水平，表明癌症干样群体被下调。在MitoSOX染色中，Cordycepin还增强了吉西他滨介导的氧化损伤，这与Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)表达比上调有关。在SNU478异种移植模型中，联合使用虫草素和吉西他滨可延缓肿瘤生长。这些结果表明，虫草素能增强吉西他滨对CCA的化疗作用，而吉西他滨的化疗作用来自于下调其癌干样特性。因此，虫草素和吉西他滨的联合治疗可能是治疗CCA的一种有前景的治疗策略。
{"title":"Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties.","authors":"Hong Kyu Lee, Yun-Jung Na, Su-Min Seong, Dohee Ahn, Kyung-Chul Choi","doi":"10.4062/biomolther.2023.198","DOIUrl":"https://doi.org/10.4062/biomolther.2023.198","url":null,"abstract":"Cordycepin, a valuable bioactive component isolated from <i>Cordyceps militaris</i>, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44<sup>high</sup>CD133<sup>high</sup> population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570391","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 : 2024-04-09DOI: 10.4062/biomolther.2023.175
Cheol Park, Hee-Jae Cha, Hyun Hwangbo, EunJin Bang, Heui-Soo Kim, Seok Joong Yun, Sung-Kwon Moon, Wun-Jae Kim, Gi-Young Kim, Seung-On Lee, Jung-Hyun Shim, Yung Hyun Choi
Mangiferin is a kind of natural xanthone glycosides and is known to have various pharmacological activities. However, since the beneficial efficacy of this compound has not been reported in retinal pigment epithelial (RPE) cells, this study aimed to evaluate whether mangiferin could protect human RPE ARPE-19 cells from oxidative injury mimicked by hydrogen peroxide (H2O2). The results showed that mangiferin attenuated H2O2-induced cell viability reduction and DNA damage, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione (GSH). Mangiferin also antagonized H2O2-induced inhibition of the expression and activity of antioxidant enzymes such as manganese superoxide dismutase and GSH peroxidase, which was associated with inhibition of mitochondrial ROS production. In addition, mangiferin protected ARPE-19 cells from H2O2-induced apoptosis by increasing the Bcl-2/Bax ratio, decreasing caspase-3 activation, and blocking poly(ADP-ribose) polymerase cleavage. Moreover, mangiferin suppressed the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Furthermore, mangiferin increased the expression and activity of heme oxygenase-1 (HO-1) and nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the inhibition of ROS production, cytoprotective and anti-apoptotic effects of mangiferin were significantly attenuated by the HO-1 inhibitor, indicating that mangiferin promoted Nrf2-mediated HO-1 activity to prevent ARPE-19 cells from oxidative injury. The results of this study suggest that mangiferin, as an Nrf2 activator, has potent ROS scavenging activity and may have the potential to protect oxidative stress-mediated ocular diseases.
{"title":"Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage.","authors":"Cheol Park, Hee-Jae Cha, Hyun Hwangbo, EunJin Bang, Heui-Soo Kim, Seok Joong Yun, Sung-Kwon Moon, Wun-Jae Kim, Gi-Young Kim, Seung-On Lee, Jung-Hyun Shim, Yung Hyun Choi","doi":"10.4062/biomolther.2023.175","DOIUrl":"https://doi.org/10.4062/biomolther.2023.175","url":null,"abstract":"Mangiferin is a kind of natural xanthone glycosides and is known to have various pharmacological activities. However, since the beneficial efficacy of this compound has not been reported in retinal pigment epithelial (RPE) cells, this study aimed to evaluate whether mangiferin could protect human RPE ARPE-19 cells from oxidative injury mimicked by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). The results showed that mangiferin attenuated H<sub>2</sub>O<sub>2</sub>-induced cell viability reduction and DNA damage, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione (GSH). Mangiferin also antagonized H<sub>2</sub>O<sub>2</sub>-induced inhibition of the expression and activity of antioxidant enzymes such as manganese superoxide dismutase and GSH peroxidase, which was associated with inhibition of mitochondrial ROS production. In addition, mangiferin protected ARPE-19 cells from H<sub>2</sub>O<sub>2</sub>-induced apoptosis by increasing the Bcl-2/Bax ratio, decreasing caspase-3 activation, and blocking poly(ADP-ribose) polymerase cleavage. Moreover, mangiferin suppressed the release of cytochrome <i>c</i> into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Furthermore, mangiferin increased the expression and activity of heme oxygenase-1 (HO-1) and nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the inhibition of ROS production, cytoprotective and anti-apoptotic effects of mangiferin were significantly attenuated by the HO-1 inhibitor, indicating that mangiferin promoted Nrf2-mediated HO-1 activity to prevent ARPE-19 cells from oxidative injury. The results of this study suggest that mangiferin, as an Nrf2 activator, has potent ROS scavenging activity and may have the potential to protect oxidative stress-mediated ocular diseases.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570199","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}
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