EXCLI Journal最新文献_第9页

Clusterin: a double-edged sword in cancer and neurological disorders. 群集素：癌症和神经系统疾病的双刃剑

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-07-09 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7369

Pinky Sultana, Jiri Novotny

{"title":"Clusterin: a double-edged sword in cancer and neurological disorders.","authors":"Pinky Sultana, Jiri Novotny","doi":"10.17179/excli2024-7369","DOIUrl":"https://doi.org/10.17179/excli2024-7369","url":null,"abstract":"Clusterin is a ubiquitously expressed glycoprotein that is involved in a whole range of biological processes. This protein is known to promote tumor survival and resistance to therapy in cancer, which contrasts sharply with its neuroprotective functions in various neurological diseases. This duality has led to recent investigations into the potential therapeutic applications of clusterin inhibition, particularly in cancer treatment. Inhibition of clusterin has been shown to be able to induce cancer cell senescence, suppress their growth and increase their sensitivity to therapy. The involvement of clusterin in the aging process makes its biological effects even more complex and offers a broad perspective for research and therapeutic exploration of various pathological conditions. This review critically examines the multiple functions of clusterin in cancer and neurological disorders and addresses the controversies surrounding its role in these areas. The assessment includes an in-depth analysis of the existing literature and examining the relationship of clusterin to fundamental aspects of cancer progression, including cell proliferation, apoptosis, metastasis, and drug resistance. In addition, the review addresses the neurobiological implications of clusterin and examines its controversial role in neuroprotection, neurodegeneration, and synaptic plasticity. Attention is also paid to the epigenetic regulation of clusterin expression. By clarifying conflicting findings and discrepancies in the literature, this review aims to provide a nuanced understanding of the molecular mechanisms underlying clusterin functions and its potential clinical implications in both cancer and neurodisorders. See also the graphical abstract(Fig. 1).","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"912-936"},"PeriodicalIF":3.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deaths among young people in England increased significantly in 10 of 11 weeks after COVID-19 vaccination and doubled in three. 在英格兰，接种 COVID-19 疫苗后的 11 周内，有 10 周的青少年死亡人数显著增加，有 3 周的死亡人数增加了一倍。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-07-04 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7498

Jarle Aarstad

引用次数: 0

Curcumin liposomes attenuate the expression of cigarette smoke extract-induced inflammatory markers IL-8 and IL-24 in vitro. 姜黄素脂质体在体外可减轻香烟烟雾提取物诱导的炎症标志物 IL-8 和 IL-24 的表达。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-06-12 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7467

Vyoma K Patel, Sofia Kokkinis, Gabriele De Rubis, Philip Michael Hansbro, Keshav Raj Paudel, Kamal Dua

引用次数: 0

Unveiling the Ro60-Ro52 complex. 揭开 Ro60-Ro52 建筑群的神秘面纱。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-06-10 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7141

Laura R Rodríguez, Jesus Vicente de Julián-Ortiz, Fernando Rubio de la Rúa, Augusto Juste-Dolz, Ángel Maquieira, Haydar A Mohammad-Salim, Sofiane Benmetir, Federico V Pallardó, Pilar González-Cabo, David Gimenez-Romero

{"title":"Unveiling the Ro60-Ro52 complex.","authors":"Laura R Rodríguez, Jesus Vicente de Julián-Ortiz, Fernando Rubio de la Rúa, Augusto Juste-Dolz, Ángel Maquieira, Haydar A Mohammad-Salim, Sofiane Benmetir, Federico V Pallardó, Pilar González-Cabo, David Gimenez-Romero","doi":"10.17179/excli2024-7141","DOIUrl":"10.17179/excli2024-7141","url":null,"abstract":"The coexistence within a subcellular complex of inter-cellular proteins Ro60, responsible for preserving ncRNA quality, and Ro52, involved in intracellular proteolysis, has been a subject of ongoing debate. Employing molecular docking in tandem with experimental methods like Quartz Crystal Microbalance with Dissipation (QCM-D), Proximity Ligation Assay (PLA), and Indirect Immunofluorescence (IIF), we reveal the presence of Ro60 associating with Ro52 within the cytoplasm. This result unveils the formation of a weak transient complex with a Ka ≈ (3.7 ± 0.3) x 106 M-1, where the toroid-shaped Ro60 structure interacts with the Ro52's Fc receptor, aligning horizontally within the PRY-SPRY domains of the Ro52's homodimer. The stability of this complex relies on the interaction between Ro52 chain A and specific Ro60 residues, such as K133, W177, or L185, vital in the Ro60-YRNA bond. These findings bridge the role of Ro60 in YRNA management with Ro52's function in intracellular proteolysis, emphasizing the potential impact of transient complexes on cellular pathways. See also the graphical abstract(Fig. 1).","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"888-903"},"PeriodicalIF":3.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

To combat poor quality research, eliminate publication requirements. 为打击劣质研究，应取消发表论文的要求。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-06-07 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7428

James Stacey Taylor

引用次数: 0

Cancer therapy by cyclin-dependent kinase inhibitors (CDKIs): bench to bedside. 细胞周期蛋白依赖性激酶抑制剂（CDKIs）的癌症治疗：从实验室到临床。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-06-04 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7076

Ali Hassanzadeh, Navid Shomali, Amin Kamrani, Mohammad Sadegh Soltani-Zangbar, Hadi Nasiri, Morteza Akbari

{"title":"Cancer therapy by cyclin-dependent kinase inhibitors (CDKIs): bench to bedside.","authors":"Ali Hassanzadeh, Navid Shomali, Amin Kamrani, Mohammad Sadegh Soltani-Zangbar, Hadi Nasiri, Morteza Akbari","doi":"10.17179/excli2024-7076","DOIUrl":"10.17179/excli2024-7076","url":null,"abstract":"A major characteristic of cancer is dysregulated cell division, which results in aberrant growth of cells. Consequently, medicinal targets that prevent cell division would be useful in the fight against cancer. The primary regulator of proliferation is a complex consisting of cyclin and cyclin-dependent kinases (CDKs). The FDA has granted approval for CDK inhibitors (CDKIs) to treat metastatic hormone receptor-positive breast cancer. Specifically, CDK4/6 CDKIs block the enzyme activity of CDK4 and CDK6. Unfortunately, the majority of first-generation CDK inhibitors, also known as pan-CDK inhibitors because they target multiple CDKs, have not been authorized for clinical use owing to their serious side effects and lack of selection. In contrast to this, significant advancements have been created to permit the use of pan-CDK inhibitors in therapeutic settings. Notably, the toxicity and negative consequences of pan-CDK inhibitors have been lessened in recent years thanks to the emergence of combination therapy tactics. Therefore, pan-CDK inhibitors have renewed promise for clinical use when used in a combination regimen. The members of the CDK family have been reviewed and their primary roles in cell cycle regulation were covered in this review. Next, we provided an overview of the state of studies on CDK inhibitors.","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"862-882"},"PeriodicalIF":3.8,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Forkhead Box O (FOXO) signaling in NSCLC: pathways to targeted therapies. NSCLC 中的叉头框 O (FOXO) 信号转导：靶向疗法的途径。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-05-31 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7272

Lakshmi Thangavelu, Terezinha de Jesus Andreoli Pinto, Sachchidanand Pathak, Abhishek Tiwari, Varsha Tiwari, Gaurav Gupta, Kumud Pant, Saurabh Gupta, Moyad Shahwan

引用次数: 0

The most dreadful mushroom toxins: a review of their toxicological mechanisms, chemical structural characteristics, and treatment. 最可怕的蘑菇毒素：毒理机制、化学结构特征和治疗方法综述。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-05-28 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7257

Irene Gouvinhas, Jani Silva, Maria José Alves, Juliana Garcia

{"title":"The most dreadful mushroom toxins: a review of their toxicological mechanisms, chemical structural characteristics, and treatment.","authors":"Irene Gouvinhas, Jani Silva, Maria José Alves, Juliana Garcia","doi":"10.17179/excli2024-7257","DOIUrl":"10.17179/excli2024-7257","url":null,"abstract":"Mushroom consumption is a worldwide custom that continues to grow in popularity. On the other hand, foraging for wild mushrooms can lead to serious disease and even death if deadly mushrooms are accidentally consumed. Mushroom poisoning is difficult to diagnose and treat since the symptoms are similar to those of other disorders. In terms of chemistry, mushroom poisoning is associated with extraordinarily strong toxins, meaning that isolating and identifying toxins has substantial scientific relevance, especially in understanding the lethal components of toxic mushrooms. Most of these toxins exhibit exceptional physiological features that might help enhance chemistry, biochemistry, physiology, and pharmacology research. Despite the discovery of more than 100 poisons, several dangerous mushrooms remain unexplored. This review covers the chemistry (including chemical structures, complete synthesis, and biosynthesis), as well as the toxicology, namely the toxicokinetics, mechanisms of toxicology, and clinical toxicology of these poisons, in addition to the discussion of the development of their most effective diagnostic and therapeutic strategies with the hopes of spurring additional studies, focusing on individual classes of toxins found in poisonous mushrooms such as amatoxins, gyromitrin, orellanine, and phallatoxins. See also the graphical abstract(Fig. 1).","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"833-859"},"PeriodicalIF":3.8,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computer-guided design of novel nitrogen-based heterocyclic sphingosine-1-phosphate (S1P) activators as osteoanabolic agents. 计算机辅助设计新型氮基杂环鞘氨醇-1-磷酸（S1P）激活剂作为骨合成代谢剂。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-05-27 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7214

Rattanawan Tangporncharoen, Chuleeporn Phanus-Umporn, Supaluk Prachayasittikul, Chanin Nantasenamat, Veda Prachayasittikul, Aungkura Supokawej

{"title":"Computer-guided design of novel nitrogen-based heterocyclic sphingosine-1-phosphate (S1P) activators as osteoanabolic agents.","authors":"Rattanawan Tangporncharoen, Chuleeporn Phanus-Umporn, Supaluk Prachayasittikul, Chanin Nantasenamat, Veda Prachayasittikul, Aungkura Supokawej","doi":"10.17179/excli2024-7214","DOIUrl":"10.17179/excli2024-7214","url":null,"abstract":"Osteoanabolic agents, or drugs that promote bone formation, have gained considerable attention for osteoporosis management due to their curative and preventive potentials. Sphingosine-1-phosphate receptor 2 (S1PR2) is an attractive drug target, in which its activation leads to osteogenesis-promoting effect. Nitrogen-containing heterocyclic scaffolds (i.e., quinoxaline and indole) are promising pharmacophores possessing diverse bioactivities and were reported as S1PR2 activators. Quantitative structure-activity relationship (QSAR) modeling is a computational approach well-known as a fundamental tool for facilitating successful drug development. This study demonstrates the discovery of new S1PR2 activators using computational-driven rational design. Herein, an original dataset of nitrogen-containing S1PR2 activators was collected from ChEMBL database. The retrieved dataset was separated into two datasets according to their core scaffolds (i.e., quinoxaline and indole). QSAR modeling was performed using multiple linear regression (MLR) algorithm to successfully obtain two models with good predictive performance. The constructed models also revealed key properties playing essential roles for potent S1PR2 activation, such as Van der Waals volume (R2v+ and E3v), mass (MATS5m and Km), electronegativity (H3e), and number of 5-membered rings (nR05). Subsequently, the constructed models were further employed to guide rational design and predict S1PR2 activating effects of an additional set of 752 structurally modified compounds. Most of the modified compounds were predicted to have higher potency than their parents, and a set of promising potent newly designed compounds was highlighted. Additionally, drug-likeness prediction was performed to reveal that most of the newly designed compounds are druggable compounds with possibility for further development.","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"818-832"},"PeriodicalIF":3.8,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Notice of retraction: Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS). 撤回通知：金合欢素诱导人恶性胶质母细胞瘤（U87）细胞的细胞毒性机制：活性氧（ROS）的作用。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-05-23 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7418

Amir R Afshari, Mohammad Jalili-Nik, Mohammad Soukhtanloo, Ahmad Ghorbani, Hamid R Sadeghnia, Hamid Mollazadeh, Mostafa Karimi Roshan, Farzad Rahmani, Hamed Sabri, Mohammad Mahdi Vahedi, Seyed Hadi Mousavi

引用次数: 0