Biomolecules & Therapeutics最新文献

Epigenetic Regulation of Nuclear Factor Erythroid-2-Related Factor 2 in Colorectal Cancer Cells Resistant to Ionizing Radiation.

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-23 DOI: 10.4062/biomolther.2024.183

Kyoung Ah Kang, Jinny Park, Mei Jing Piao, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna, Jung-Hwan Kim, Suk Ju Cho, Jin Won Hyun

{"title":"Epigenetic Regulation of Nuclear Factor Erythroid-2-Related Factor 2 in Colorectal Cancer Cells Resistant to Ionizing Radiation.","authors":"Kyoung Ah Kang, Jinny Park, Mei Jing Piao, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna, Jung-Hwan Kim, Suk Ju Cho, Jin Won Hyun","doi":"10.4062/biomolther.2024.183","DOIUrl":"https://doi.org/10.4062/biomolther.2024.183","url":null,"abstract":"γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the NRF2 promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the NRF2 promoter. TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876059","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}

引用次数: 0

The Dual Role of Survival Genes in Neurons and Cancer Cells: a Strategic Clinical Application of DX2 in Neurodegenerative Diseases and Cancer.

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-23 DOI: 10.4062/biomolther.2024.138

Kyunghwa Baek

{"title":"The Dual Role of Survival Genes in Neurons and Cancer Cells: a Strategic Clinical Application of DX2 in Neurodegenerative Diseases and Cancer.","authors":"Kyunghwa Baek","doi":"10.4062/biomolther.2024.138","DOIUrl":"https://doi.org/10.4062/biomolther.2024.138","url":null,"abstract":"In cancer cells, survival genes contribute to uncontrolled growth and the survival of malignant cells, leading to tumor progression. Neurons are post-mitotic cells, fully differentiated and non-dividing after neurogenesis and survival genes are essential for cellular longevity and proper functioning of the nervous system. This review explores recent research findings regarding the role of survival genes, particularly DX2, in degenerative neuronal tissue cells and cancer cells. Survival gene DX2, an exon 2-deleted splice variant of AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), was found to be overexpressed in various cancer types. The potential of DX2 inhibitors as an anti-cancer drug arises from its unique ability to interact with various oncoproteins, such as KRAS and HSP70. Meanwhile, AIMP2 has been reported as a multifunctional cell death-inducing gene, and survival gene DX2 directly and indirectly inhibits AIMP2-induced cell death. DX2 plays multifaceted survival roles in degenerating neurons via various signaling pathways, including PARP 1, TRAF2, and p53 pathways. It is noteworthy that genes that were previously classified as oncogenes, such as AKT and XBP1, are now being considered as curative transgenes for targeting neurodegenerative diseases. A strategic direction for clinical application of survival genes in neurogenerative disease and in cancer is justified.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876071","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}

引用次数: 0

New Insights into AMPK, as a Potential Therapeutic Target in Metabolic Dysfunction-Associated Steatotic Liver Disease and Hepatic Fibrosis. AMPK 作为代谢功能障碍相关性脂肪肝和肝纤维化潜在治疗靶点的新见解。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-20 DOI: 10.4062/biomolther.2024.188

Haeun An, Yerin Jang, Jungin Choi, Juhee Hur, Seojeong Kim, Youngjoo Kwon

{"title":"New Insights into AMPK, as a Potential Therapeutic Target in Metabolic Dysfunction-Associated Steatotic Liver Disease and Hepatic Fibrosis.","authors":"Haeun An, Yerin Jang, Jungin Choi, Juhee Hur, Seojeong Kim, Youngjoo Kwon","doi":"10.4062/biomolther.2024.188","DOIUrl":"https://doi.org/10.4062/biomolther.2024.188","url":null,"abstract":"AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into liver fibrosis and to fundamentally improve liver function. The broad spectrum of pathways regulated by AMPK activators makes them promising alternatives to conventional liver replacement therapies and the limited pharmacological treatments currently available. In this study, we aim to illustrate the newly detailed multiple mechanisms of MASLD progression based on the multiple-hit hypothesis. This model posits that impaired lipid metabolism, combined with insulin resistance and metabolic imbalance, initiates inflammatory cascades, gut dysbiosis, and the accumulation of toxic metabolites, ultimately promoting fibrosis and accelerating MASLD progression to irreversible hepatocellular carcinoma (HCC). AMPK plays a multifaceted protective role against these pathological conditions by regulating several key downstream signaling pathways. It regulates biological effectors critical to metabolic and inflammatory responses, such as SIRT1, Nrf2, mTOR, and TGF-β, through complex and interrelated mechanisms. Due to these intricate connections, AMPK's role is pivotal in managing metabolic and inflammatory disorders. In this review, we demonstrate the specific roles of AMPK and its related pathways. Several agents directly activate AMPK by binding as agonists, while some others indirectly activate AMPK by modulating upstream molecules, including adiponectin, LKB1, and the AMP: ATP ratio. As AMPK activators can target each stage of MASLD progression, the development of AMPK activators offers immense potential to expand therapeutic strategies for liver diseases such as MASH, MASLD, and liver fibrosis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862958","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}

引用次数: 0

An Overview of Existing and Emerging Weight-Loss Drugs to Target Obesity-Related Complications: Insights from Clinical Trials.

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-19 DOI: 10.4062/biomolther.2024.228

Mi Kyung Kim, Hye Soon Kim

引用次数: 0

C-Peptide Ameliorates Particulate Matter 2.5-Induced Skin Cell Apoptosis by Inhibiting NADPH Oxidation.

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-18 DOI: 10.4062/biomolther.2024.053

Pincha Devage Sameera Madushan Fernando, Mei Jing Piao, Herath Mudiyanselage Udari Lakmini Herath, Kyoung Ah Kang, Kwon-Soo Ha, Sungwook Chae, Jin Won Hyun

{"title":"C-Peptide Ameliorates Particulate Matter 2.5-Induced Skin Cell Apoptosis by Inhibiting NADPH Oxidation.","authors":"Pincha Devage Sameera Madushan Fernando, Mei Jing Piao, Herath Mudiyanselage Udari Lakmini Herath, Kyoung Ah Kang, Kwon-Soo Ha, Sungwook Chae, Jin Won Hyun","doi":"10.4062/biomolther.2024.053","DOIUrl":"https://doi.org/10.4062/biomolther.2024.053","url":null,"abstract":"Connecting peptide (C-peptide), a byproduct of insulin biosynthesis, has diverse cellular and biological functions. Particulate matter 2.5 (PM2.5) adversely affects human skin, leading to skin thickening, wrinkle formation, skin aging, and inflammation. This study aimed to investigate the protective effects of C-peptide against PM2.5-induced damage to skin cells, focusing on oxidative stress as a key mechanism. C-peptide mitigated NADPH oxidation and intracellular reactive oxygen species (ROS) production induced by PM2.5. It also suppressed PM2.5-induced NADPH oxidase (NOX) activity and alleviated PM2.5-induced NOX1 and NOX4 expression. C-peptide protected against PM2.5-induced DNA damage, lipid peroxidation, and protein carbonylation. Additionally, C-peptide mitigated PM2.5-induced apoptosis by inhibiting intracellular ROS production. In summary, our findings suggest that C-peptide mitigates PM2.5-induced apoptosis in human HaCaT keratinocytes by inhibiting intracellular ROS production and NOX activity.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845759","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}

引用次数: 0

Probiotics as Potential Treatments for Neurodegenerative Diseases: a Review of the Evidence from in vivo to Clinical Trial.

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-16 DOI: 10.4062/biomolther.2024.215

Jin Hee Kim, Yujin Choi, Seungmin Lee, Myung Sook Oh

{"title":"Probiotics as Potential Treatments for Neurodegenerative Diseases: a Review of the Evidence from in vivo to Clinical Trial.","authors":"Jin Hee Kim, Yujin Choi, Seungmin Lee, Myung Sook Oh","doi":"10.4062/biomolther.2024.215","DOIUrl":"https://doi.org/10.4062/biomolther.2024.215","url":null,"abstract":"Neurodegenerative diseases (NDDs), characterized by the progressive deterioration of the structure and function of the nervous system, represent a significant global health challenge. Emerging research suggests that the gut microbiota plays a critical role in regulating neurodegeneration via modulation of the gut-brain axis. Probiotics, defined as live microorganisms that confer health benefits to the host, have garnered significant attention owing to their therapeutic potential in NDDs. This review examines the current research trends related to the microbiome-gut-brain axis across various NDDs, highlighting key findings and their implications. Additionally, the effects of specific probiotic strains, including Lactobacillus plantarum, Bifidobacterium breve, and Lactobacillus rhamnosus, on neurodegenerative processes were assessed, focusing on their potential therapeutic benefits. Overall, this review emphasizes the potential of probiotics as promising therapeutic agents for NDDs, underscoring the importance of further investigation into this emerging field.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827096","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}

引用次数: 0

Hepatoprotective Effects of Resveratrol on Acetaminophen-Induced Acute Liver Injury and Its Implications for Tofacitinib Disposition in Rats.

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-13 DOI: 10.4062/biomolther.2024.184

Hyeon Gyeom Choi, So Yeon Park, Sung Hun Bae, Sun-Young Chang, So Hee Kim

{"title":"Hepatoprotective Effects of Resveratrol on Acetaminophen-Induced Acute Liver Injury and Its Implications for Tofacitinib Disposition in Rats.","authors":"Hyeon Gyeom Choi, So Yeon Park, Sung Hun Bae, Sun-Young Chang, So Hee Kim","doi":"10.4062/biomolther.2024.184","DOIUrl":"https://doi.org/10.4062/biomolther.2024.184","url":null,"abstract":"Tofacitinib, which is used to treat rheumatoid arthritis (RA), is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, CYP3A1/2 and CYP2C11. Acetaminophen (APAP), which is frequently used for pain relief in patients with RA, can induce acute liver injury (ALI) when taken in excess, profoundly affecting drug metabolism. Resveratrol (RVT) is a polyphenolic compound with hepatoprotective properties. This study investigated the protective effects of RVT against APAP-induced ALI in rats, and explored its influence on the pharmacokinetics of tofacitinib. In ALI rats, both intravenous and oral administration of tofacitinib resulted in a significant (207% and 181%) increase in the area under the plasma concentration-time curve (AUC), primarily driven by a substantial reduction (66.1%) in non-renal clearance (CLNR) compared to that in control (CON) rats. Notably, RVT administration in ALI rats provided effective liver protection, partially restoring liver function, as evidenced by normalized glutamate oxaloacetate transaminase levels and the pharmacokinetic parameters, AUC and CLNR, closer to those observed in untreated CON rats (117% and 81.9%, respectively). These findings highlight the importance of considering the potential interactions between RVT or polyphenol-rich natural products and medications in patients with ALI in clinical practice.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817057","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}

引用次数: 0

The Emerging Threat of Micro- and Nanoplastics on the Maturation and Activity of Immune Cells.

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-12 DOI: 10.4062/biomolther.2024.195

Kang-Bin Dan, Ji Yoon Yoo, Hyeyoung Min

引用次数: 0

Translationally Controlled Tumor Protein Enhances Angiogenesis in Ovarian Tumors by Activating Vascular Endothelial Growth Factor Receptor 2 Signaling.

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-12 DOI: 10.4062/biomolther.2024.206

Seung Bae Rho, Boh-Ram Kim, Seung-Hoon Lee, Chang Hoon Lee

{"title":"Translationally Controlled Tumor Protein Enhances Angiogenesis in Ovarian Tumors by Activating Vascular Endothelial Growth Factor Receptor 2 Signaling.","authors":"Seung Bae Rho, Boh-Ram Kim, Seung-Hoon Lee, Chang Hoon Lee","doi":"10.4062/biomolther.2024.206","DOIUrl":"https://doi.org/10.4062/biomolther.2024.206","url":null,"abstract":"Translationally controlled tumor protein (TCTP) is a regulatory protein that plays pivotal roles in cellular processes including the cell cycle, apoptosis, microtubule stabilization, embryo development, stress responses, and cancer. However, the molecular mechanism by which it promotes tumor angiogenesis is still unclear. In this study, we explored the mechanisms underlying stimulation of angiogenesis by a novel TCTP. Recombinant TCTP enhanced vascular endothelial growth factor (VEGF)-induced endothelial cell migration, capillary-like tubular structure formation, and cell proliferation by interacting with VEGF receptor 2 (VEGFR-2) in vitro. In contrast, we showed that TCTP knockdown (using short interfering [si]TCTP) led to a decrease in ovarian tumor cells. We also examined the expression of VEGF and hypoxia inducible factor 1 (HIF-1α), an important angiogenic factor. The expression of VEGF as well as HIF-1α was dramatically decreased by siTCTP. Mechanistically, siTCTP inhibited VEGFR-2 tyrosine phosphorylation and phosphorylation of its downstream targets PI3K, Akt, and mTOR. Collectively, these findings indicate that TCTP can promote proliferation and angiogenesis via the VEGFR-2/PI3K and mTOR signaling pathways in ovarian tumor cells, providing new insight into the mechanism behind the involvement of TCTP in tumor angiogenesis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811959","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}

引用次数: 0

Tanshinone, a Natural NADPH Oxidase Inhibitor, Mitigates Testosterone-Induced Hair Loss.

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-12-05 DOI: 10.4062/biomolther.2024.097

Yeo Kyu Hur, Jin Yeong Chae, Min Hye Choi, Kkotnara Park, Da-Woon Bae, Soo-Bong Park, Sun-Shin Cha, Hye Eun Lee, In Hye Lee, Yun Soo Bae

{"title":"Tanshinone, a Natural NADPH Oxidase Inhibitor, Mitigates Testosterone-Induced Hair Loss.","authors":"Yeo Kyu Hur, Jin Yeong Chae, Min Hye Choi, Kkotnara Park, Da-Woon Bae, Soo-Bong Park, Sun-Shin Cha, Hye Eun Lee, In Hye Lee, Yun Soo Bae","doi":"10.4062/biomolther.2024.097","DOIUrl":"https://doi.org/10.4062/biomolther.2024.097","url":null,"abstract":"Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H2O2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779278","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}

引用次数: 0