Current Research in Pharmacology and Drug Discovery最新文献

{"title":"Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies","authors":"Emeka Eze Joshua Iweala ,&nbsp;Doris Nnenna Amuji ,&nbsp;Abimbola Mary Oluwajembola ,&nbsp;Eziuche Amadike Ugbogu","doi":"10.1016/j.crphar.2024.100204","DOIUrl":"10.1016/j.crphar.2024.100204","url":null,"abstract":"<div><div>Breast cancer presents a significant challenge due to its heterogeneity and propensity for developing chemoresistance, particularly in the triple-negative subtype. c-Mesenchymal epithelial transition factor (c-Met), a receptor tyrosine kinase, presents a promising target for breast cancer therapy due to its involvement in disease progression and poor prognosis. However, the heterogeneous expression of c-Met within breast cancer subtypes and individual tumors complicates targeted therapy. Also, cancer cells can develop resistance to c-Met inhibitors through various mechanisms, including bypass signaling pathways and genetic mutations. The off-target effects of c-Met inhibitors further limit their clinical utility, necessitating the development of more selective agents. To overcome these challenges, personalized treatment approaches and combination therapies are being explored to improve treatment efficacy while minimizing adverse effects. Novel c-Met inhibitors with improved selectivity and reduced off-target toxicity show promise in preclinical studies. Additionally, targeted delivery systems aim to enhance drug localization and reduce systemic toxicity. Future directions involve refining inhibitor design and integrating c-Met inhibition into personalized treatment regimens guided by molecular profiling. This review explores the mechanisms by which c-Met contributes to chemoresistance in breast cancer and current challenges in targeting c-Met for breast cancer therapy. It discusses strategies to optimize treatment outcomes, ultimately improving patient prognosis and reducing mortality rates associated with this devastating disease.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"7 ","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142527348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liraglutide improves adipose tissue remodeling and mitochondrial dynamics in a visceral obesity model induced by a high-fat diet","authors":"Vanessa Touceda ,&nbsp;Florencia Fontana Estevez ,&nbsp;Leonardo Cacciagiú ,&nbsp;Paola Finocchietto ,&nbsp;Romina Bustos ,&nbsp;Agustina Vidal ,&nbsp;Gabriela Berg ,&nbsp;Celina Morales ,&nbsp;Germán González ,&nbsp;Veronica Miksztowicz","doi":"10.1016/j.crphar.2024.100185","DOIUrl":"10.1016/j.crphar.2024.100185","url":null,"abstract":"<div><p>Central obesity is characterized by visceral adipose tissue (VAT) expansion, considered one of the main risk factors for metabolic complications. In recent years, new drugs have been studied for obesity treatment. Liraglutide (LGT), a GLP-1 agonist, decreases body weight, however, several mechanisms of action on VAT are still unknown.</p></div><div><h3>Aim</h3><p>to study the effect of LGT on factors associated with VAT remodeling and mitochondrial dynamics in mice fed a high-fat diet (HFD).</p></div><div><h3>Methods</h3><p>C57BL/6 mice were divided into Control (C) and HFD. After 15 weeks of feeding, each group was subdivided according to LGT administration for 5 weeks: C, C + LGT, HFD, and HFD + LGT. In epididymal AT (EAT) we evaluated histological and mitochondrial characteristics, vascularity, gelatinase activity (MMPs), and galectin-3 expression.</p></div><div><h3>Results</h3><p>HFD presented larger adipocytes (p &lt; 0.05), and lower vascular density and MMP-9 activity (p &lt; 0.01) than C, while a major number of smaller adipocytes (p &lt; 0.05) and an increase in vascularity (p &lt; 0.001) and MMP-9 activity (p &lt; 0.01) was observed in HFD + LGT. Collagen content was higher (p &lt; 0.05) in EAT from HFD and decreased in HFD + LGT. In C, C + LGT, and HFD + LGT, mitochondria were predominantly tubular-shaped while in HFD mitochondria were mostly spherical (p &lt; 0.001).</p></div><div><h3>Conclusion</h3><p>LGT positively influences VAT behavior by modulating gelatinase activity, enhancing vascularization, and improving adipocyte histological characteristics. Additionally, LGT improves mitochondrial dynamics, a process that would favor VAT functionality.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"6 ","pages":"Article 100185"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000129/pdfft?md5=2d5a86602bcffd980508a12e69fbcb26&pid=1-s2.0-S2590257124000129-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141130313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of miRNA-based approaches in glioblastoma: An update in current advances and future perspectives","authors":"Edgar G. Ordóñez-Rubiano MD, PhD (c) ,&nbsp;Nicolás Rincón-Arias MD ,&nbsp;Sebastian Espinosa MD ,&nbsp;William J. Shelton MD ,&nbsp;Andres F. Salazar ,&nbsp;Alba Cómbita MSc, PhD ,&nbsp;Matías Baldoncini MD ,&nbsp;Sabino Luzzi MD, PhD ,&nbsp;César Payán-Gómez MD, PhD ,&nbsp;Diego F. Gómez- Amarillo MD, MSc ,&nbsp;Fernando Hakim MD ,&nbsp;Javier G. Patiño-Gómez MD ,&nbsp;Rafael Parra- Medina MD, PhD","doi":"10.1016/j.crphar.2024.100193","DOIUrl":"https://doi.org/10.1016/j.crphar.2024.100193","url":null,"abstract":"<div><p>Glioblastoma (GBM) is the most common malignant central nervous system tumor. The emerging field of epigenetics stands out as particularly promising. Notably, the discovery of micro RNAs (miRNAs) has paved the way for advancements in diagnosing, treating, and prognosticating patients with brain tumors. We aim to provide an overview of the emergence of miRNAs in GBM and their potential role in the multifaceted management of this disease. We discuss the current state of the art regarding miRNAs and GBM. We performed a narrative review using the MEDLINE/PUBMED database to retrieve peer-reviewed articles related to the use of miRNA approaches for the treatment of GBMs. MiRNAs are intrinsic non-coding RNA molecules that regulate gene expression mainly through post-transcriptional mechanisms. The deregulation of some of these molecules is related to the pathogenesis of GBM. The inclusion of molecular characterization for the diagnosis of brain tumors and the advent of less-invasive diagnostic methods such as liquid biopsies, highlights the potential of these molecules as biomarkers for guiding the management of brain tumors such as GBM. Importantly, there is a need for more studies to better examine the application of these novel molecules. The constantly changing characterization and approach to the diagnosis and management of brain tumors broaden the possibilities for the molecular inclusion of novel epigenetic molecules, such as miRNAs, for a better understanding of this disease.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"7 ","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000208/pdfft?md5=e3fb5cee84b6f649ec2a936785e8f6e2&pid=1-s2.0-S2590257124000208-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141540070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Recombinant Antibody by Yeast Surface Display Technology","authors":"Mujahed I. Mustafa ,&nbsp;Awad A. Alzebair ,&nbsp;Ahmed Mohammed","doi":"10.1016/j.crphar.2024.100174","DOIUrl":"10.1016/j.crphar.2024.100174","url":null,"abstract":"<div><p>Recombinant antibodies have emerged as powerful tools in various fields, including therapeutics, diagnostics, and research applications. The selection of high-affinity antibodies with desired specificity is a crucial step in the development of recombinant antibody-based products. In recent years, yeast surface display technology has gained significant attention as a robust and versatile platform for antibody selection. This graphical review provides an overview of the yeast surface display technology and its applications in recombinant antibody selection. We discuss the key components involved in the construction of yeast surface display libraries, including the antibody gene libraries, yeast host strains, and display vectors. Furthermore, we highlight the strategies employed for affinity maturation and optimization of recombinant antibodies using yeast surface display. Finally, we discuss the advantages and limitations of this technology compared to other antibody selection methods. Overall, yeast surface display technology offers a powerful and efficient approach for the selection of recombinant antibodies, enabling the rapid generation of high-affinity antibodies for various applications.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"6 ","pages":"Article 100174"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000014/pdfft?md5=6b65539c630be8a3142504caae389fe9&pid=1-s2.0-S2590257124000014-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139632723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The novel inhaled dual PDE3 and PDE4 inhibitor ensifentrine for the treatment of COPD: A systematic review and meta-analysis protocol on trough FEV1 and exacerbation according to PRISMA statement","authors":"Luigino Calzetta ,&nbsp;Mario Cazzola ,&nbsp;Shima Gholamalishahi ,&nbsp;Paola Rogliani","doi":"10.1016/j.crphar.2024.100195","DOIUrl":"https://doi.org/10.1016/j.crphar.2024.100195","url":null,"abstract":"<div><p>The investigation of ensifentrine, an inhaled dual phosphodiesterase (PDE)3 and PDE4 inhibitor, for chronic obstructive pulmonary disease (COPD) maintenance therapy presents a significant clinical interest. Despite promising results from recent Phase III trials, a comprehensive synthesis of its therapeutic efficacy in COPD is lacking. This protocol outlines the first registered systematic review and meta-analysis in PROSPERO to assess the impact of ensifentrine on trough forced expiratory volume in the 1st second (FEV₁) and acute exacerbations of COPD. By conducting a rigorous literature search and employing solid methodologies, this endeavour aims to provide robust evidence on the real efficacy of ensifentrine. Anticipated outcomes include a significant improvement in trough FEV₁ and a reduction in AECOPD risk among ensifentrine-treated patients compared to controls, corroborating its bronchodilator and anti-inflammatory properties. The meta-analysis expects to reveal consistent results across different trials, enhancing confidence in the findings. Additionally, subgroup analyses may unveil factors influencing the efficacy of ensifentrine, guiding optimal therapeutic strategies. Overall, this protocol holds the potential to inform clinical practice and regulatory decisions, positioning ensifentrine as a valuable addition to COPD management.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"7 ","pages":"Article 100195"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000221/pdfft?md5=c1dd1dd9bb8e3d2305050b6a5ff9b591&pid=1-s2.0-S2590257124000221-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141582192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of 2-((4-(chloromethyl)benzoyl)oxy)benzoate acid for analgesic tablet dosage form formulation","authors":"Wuryanto Hadinugroho,&nbsp;Yudy Tjahjono,&nbsp;Kuncoro Foe,&nbsp;Senny Yesery Esar,&nbsp;Caroline Caroline,&nbsp;Maria Annabella Jessica,&nbsp;Hendy Wijaya","doi":"10.1016/j.crphar.2024.100200","DOIUrl":"10.1016/j.crphar.2024.100200","url":null,"abstract":"<div><p>The 2-((4-(chloromethyl)benzoyl)oxy)benzoic acid (4CH₂Cl) is a potential analgesic compound derived from salicylic acid and 4-chloromethyl benzoyl chloride. Characterization required 4CH₂Cl for the formulation of tablet dosage forms. This study aims investigate the effect of SSG, PVP-K30, and the combination of SSG*PVP K-30 on the formulation of 4CH₂Cl tablets. Additionally, this study aimed to obtain the optimum 4CH₂Cl tablet composition. The experiment followed the two-factor simplex lattice design and direct compression method. The analgesic activity of 4CH₂Cl in the optimal tablet was investigated using the hot-plate methods. The ANOVA of linear models is acceptable and the polynomial coefficients of quadratic models are similar to those of linear models. The coefficient of the linear model shows that SSG and PVP K-30 increase the Carr index (16.26; 20.61), Hausner ratio (1.19; 1.29), hardness (4.19; 9.39), friability (0.48; 0.67), disintegration time (0.34; 7.50), and drug release (85.29; 97.69). The coefficient of the quadratic model shows that SSG*PVP K-30 increased the Carr index (1.90), Hausner ratio (0.04), hardness (1.88), friability (0.06), and drug release (4.56), and decreased disintegration time (−0.30). SSG and PVP K-30 increased Carr index, Hausner ratio, hardness, friability, disintegration time, and drug release. The combination of SSG*PVP K-30 has the same effect, except that the disintegration time decreased. The optimum tablet formula is 4CH₂Cl (300 mg), Ne (75 mg), SSG (33.60 mg), PVP K-30 (22.40 mg), MCC (40 mg), and SDL (up to 800 mg). 4CH₂Cl tablets can be a candidate and choice for new analgesic drugs in the future.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"7 ","pages":"Article 100200"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000270/pdfft?md5=a80324e5d165886f3005648cc749103b&pid=1-s2.0-S2590257124000270-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell therapy as a promising approach for ischemic stroke treatment","authors":"Sahar Yaqubi,&nbsp;Mohammad Karimian","doi":"10.1016/j.crphar.2024.100183","DOIUrl":"10.1016/j.crphar.2024.100183","url":null,"abstract":"<div><p>Ischemia as the most common type of stroke is the main cause of death and disability in the world. However, there are few therapeutic approaches to treat ischemic stroke. The common approach to the treatment of ischemia includes surgery-cum-chemical drugs. Surgery and chemical drugs are used to remove blood clots to prevent the deterioration of the nervous system. Given the surgical hazards and the challenges associated with chemical drugs, these cannot be considered safe approaches to the treatment of brain ischemia. Besides surgery-cum-chemical drugs, different types of stem cells including mesenchymal stem cells and neurological stem cells have been considered to treat ischemic stroke. Therapeutic approaches utilizing stem cells to treat strokes are promising because of their neuroprotective and regenerative benefits. However, the mechanisms by which the transplanted stem cells perform their precisely actions are unknown. The purpose of this study is to critically review stem cell-based therapeutic approaches for ischemia along with related challenges.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"6 ","pages":"Article 100183"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000105/pdfft?md5=4930984c2fd48472ce800fface90619c&pid=1-s2.0-S2590257124000105-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141032993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats","authors":"Doaa Adnan Atshan ,&nbsp;Munaf Hashim Zalzala","doi":"10.1016/j.crphar.2024.100177","DOIUrl":"https://doi.org/10.1016/j.crphar.2024.100177","url":null,"abstract":"<div><p>Cholestasis is a hepatobiliary condition that manifests as acute or chronic and results from disruptions in the bile flow, formation, or secretion processes. The Farnesoid X receptor (FXR) is a vital target for the therapy of cholestasis since it regulates BA homeostasis. Despite the discovery of multiple active FXR agonists, there are still no effective treatments for cholestasis. Papaverine is identified as an FXR agonist.This study investigates papaverine's efficacy and probable mechanism in protecting against alpha naphthylisothiocyanate (ANIT) induced cholestasis. Thirty male albino rats were divided into three groups, each with ten rats. Group I (control) rats were administered 1 mL/kg corn oil 48 h before sacrifice; group II rats were orally administered 100 mg/kg ANIT. Group III received a 200 mg/kg dosage of papaverine over seven consecutive days. A single dose of ANIT at a concentration of 100 mg/kg was orally administered on the fifth day; group II and III animals were euthanized 48 h after inducing cholestasis, and serum concentrations of liver function tests and total bile acid (TBA) were measured. Besides measuring the inflammatory mediator's tumor necrosis factor-alpha (TNF-α) and interleukin 1 (IL-1β), antioxidant markers such as superoxide dismutase (SOD) and glutathione (GSH) were also assessed. The findings indicated the enhancement in the liver function test and total bile acids, as well as in liver histology; papaverine significantly lowered TNF-α and IL-1β while SOD and GSH significantly increased. Additionally, papaverine upregulates <em>Fxr</em> gene expression, bile salt export pump (<em>Besp</em>), small heterodimer partner (<em>shp</em>), hepatocyte nuclear factor 1α (<em>Hnfα</em>), nuclear factor erythroid 2-related factor (<em>Nrf2</em>), heme oxygenase (<em>Ho-1</em>), NAD(P)H quinone oxidoreductase 1 (<em>Nqo1</em>). Furthermore, papaverine increased protein expressions of Sirtuin1.</p><p>(SIRT 1), FXR, HO-1, and BSEP levels in the rats' livers. The protective effects of papaverine may be attributed to the activation of FXR signaling pathways. These findings revealed that papaverine protects against ANIT-induced Cholestasis.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"6 ","pages":"Article 100177"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259025712400004X/pdfft?md5=7649143687736ada6e8a2ab879020a7e&pid=1-s2.0-S259025712400004X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139653033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GERD: Latest update on acid-suppressant drugs","authors":"Zyad AL-Frejat ,&nbsp;Nafiza Martini ,&nbsp;Alia Esper ,&nbsp;Diana Al-Frejat ,&nbsp;Samer Younes ,&nbsp;Majd Hanna","doi":"10.1016/j.crphar.2024.100198","DOIUrl":"10.1016/j.crphar.2024.100198","url":null,"abstract":"<div><p>GERD is a very familiar diagnosis among health care providers due to its massive spread, and its symptoms can affect the quality of life for a respectable slice of its patients. Therefore, what can only be described as a logical consequence, a pursuit of a treatment that can both relieve symptoms and have minimal side effects is still ongoing to cover the large demographic affected by GERD. In the following review, analysis will be made of GERD, including possible regulatory activity, of certain drugs to the already discussed pathways involved in GERD patients.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"7 ","pages":"Article 100198"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000257/pdfft?md5=e6c868901ce49b17b1265e7cd2f8052c&pid=1-s2.0-S2590257124000257-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis induces nucleolar stress as revealed by live-cell imaging using thioflavin T","authors":"Yoko Hirata ,&nbsp;Hiroshi Takemori ,&nbsp;Kyoji Furuta ,&nbsp;Yuji O. Kamatari ,&nbsp;Makoto Sawada","doi":"10.1016/j.crphar.2024.100196","DOIUrl":"https://doi.org/10.1016/j.crphar.2024.100196","url":null,"abstract":"<div><p>Nucleolar stress induced by stressors like hypoxia, UV irradiation, and heat shock downregulates ribosomal RNA transcription, thereby impairing protein synthesis capacity and potentially contributing to cell senescence and various human diseases such as neurodegenerative disorders and cancer. Live-cell imaging of the nucleolus may be a feasible strategy for investigating nucleolar stress, but currently available nucleolar stains are limited for this application. In this study using mouse hippocampal HT22 cells, we demonstrate that thioflavin T (ThT), a benzothiazole dye that binds RNA with high affinity, is useful for nucleolar imaging in cells where RNAs predominate over protein aggregates. Nucleoli were stained with high intensity simply by adding ThT to the cell culture medium, making it suitable for use even in damaged cells. Further, ThT staining overlapped with specific nucleolar stains in both live and fixed cells, but did not overlap with markers for mitochondria, lysosomes, endoplasmic reticulum, and double-stranded DNA. Ferroptosis, an iron-dependent nonapoptotic cell death pathway characterized by lipid peroxide accumulation, reduced the number of ThT-positive puncta while endoplasmic reticulum stress did not. These findings suggest that ferroptosis is associated with oxidative damage to nucleolar RNA molecules and ensuing loss of nucleolar function.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"7 ","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000233/pdfft?md5=c1089fbc0a10fc2cfe01e0f9b383037a&pid=1-s2.0-S2590257124000233-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141582193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}