EXCLI Journal最新文献_第5页

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

Current biological and pharmacological updates on Tinospora cordifolia. 当前有关铁杉的生物学和药理学最新进展。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-05-21 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7170

Shubham Kumar, Murtaza M Tambuwala, Yachana Mishra, Vijay Mishra

引用次数: 0

Exhaled volatile organic compounds in the detection of colorectal cancer: a systematic review and meta-analysis. 检测结直肠癌的呼出挥发性有机化合物：系统回顾和荟萃分析。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-05-17 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7042

Daniah Alsaadi, Nicolle Clements, Natiya Gabuniya, Nader Francis, Manish Chand

{"title":"Exhaled volatile organic compounds in the detection of colorectal cancer: a systematic review and meta-analysis.","authors":"Daniah Alsaadi, Nicolle Clements, Natiya Gabuniya, Nader Francis, Manish Chand","doi":"10.17179/excli2024-7042","DOIUrl":"10.17179/excli2024-7042","url":null,"abstract":"There is an apparent need for novel non-invasive colorectal cancer (CRC) screening tests that are more acceptable to patients and can reliably detect CRC or reduce the number of unnecessary colonoscopies performed in cancer-free patients. An emerging number of studies demonstrate the potential value of exhaled volatile organic compounds (VOCs) as a diagnostic and triaging test for CRC. A systematic appraisal and meta-analysis of the published evidence was done to determine whether exhaled VOCs can be used in the detection and screening of CRC. Nine electronic databases were searched from inception of the databases until August 2020. Quantitative and descriptive data of CRC patients and healthy control (HC) participants who underwent VOCs breath analysis was extracted. In addition, where possible, sampling methods, analytical platforms, processors, and specific breath biomarkers found in each study were recorded. Fourteen articles were included in the systematic review with 491 colorectal patients and 754 HC participants (n=1245). Sub-group meta-analysis was conducted on nine of those articles and the pooled sensitivity was estimated to be 0.89 (95 % CI = 0.80-0.99) whereas specificity was 0.83 (95 % CI = 0.74-0.92). Heterogeneity of pooled sensitivity and specificity was estimated as I2=11.11 %. Although this study was limited by small sample size and different analytical platforms, the proposed future framework resolves such limitations and standardizes future research. It is reasonable to deduce that VOCs breath analysis is certainly a field of research that can progress to replace traditional methods within the framework of CRC screening and diagnosis.","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"795-810"},"PeriodicalIF":3.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563089","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

Recent insights into luteolin and its biological and pharmacological activities. 关于木犀草素及其生物和药理活性的最新研究成果。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-05-16 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7168

Priscilla Nadalin, Jae Kwang Kim, Sang Un Park

引用次数: 0

A regulatory compliant short-term oral toxicity study of soluble [60]fullerenes in rats. 符合法规要求的可溶性 [60] 富勒烯大鼠短期口服毒性研究。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-05-15 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7084

Christopher Burres, Robert Wong, Fabio Pedreira, Maria Da Silva Pimenta, Fathi Moussa

{"title":"A regulatory compliant short-term oral toxicity study of soluble [60]fullerenes in rats.","authors":"Christopher Burres, Robert Wong, Fabio Pedreira, Maria Da Silva Pimenta, Fathi Moussa","doi":"10.17179/excli2024-7084","DOIUrl":"10.17179/excli2024-7084","url":null,"abstract":"Thirty-eight years after its discovery, the safety of [60]fullerene (C60), the most abundant fullerene with many potential applications, particularly in oxidative stress-related medicine, remains controversial. This is mainly due to the alleged dangers of C60 nanomaterial, which are regularly supported by some publications. While several academic studies have confirmed the safety of C60 in various experimental models, it is well known that C60 aggregates can carry toxic elements. Meanwhile, countless websites offer C60-oily solutions to consumers, without any regulatory consideration. Therefore, an officially certified toxicity study is urgently needed to avoid any public health problems. In this context, we report on the first certified short-term oral toxicity study of soluble C60, designed according to the guidelines of the Organization for Economic Cooperation and Development, with a deviation in the duration (2 weeks instead of 4 weeks) accepted by the U.S. Food and Drug Administration. The results of this study, conducted in an independent accredited European Laboratory, clearly show that C60 in soluble form (0.8 mg/ml of extra virgin olive oil), administered at the highest possible dose of 3.8 mg/kg body weight/day, did not cause any adverse effects in rats after 14 days of daily oral administration. This report should settle the debate on the acute oral toxicity of C60 and pave the way for further preclinical studies. The study is accompanied by a comprehensive report that includes documentation of the raw data.","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"772-786"},"PeriodicalIF":3.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563087","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

Integrating fNIRS and machine learning: shedding light on Parkinson's disease detection. 将 fNIRS 与机器学习相结合：揭示帕金森病的检测方法。

IF 3.8 3区生物学

EXCLI Journal Pub Date : 2024-05-14 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7151

Edgar Guevara, Gabriel Solana-Lavalle, Roberto Rosas-Romero

{"title":"Integrating fNIRS and machine learning: shedding light on Parkinson's disease detection.","authors":"Edgar Guevara, Gabriel Solana-Lavalle, Roberto Rosas-Romero","doi":"10.17179/excli2024-7151","DOIUrl":"10.17179/excli2024-7151","url":null,"abstract":"The purpose of this research is to introduce an approach to assist the diagnosis of Parkinson's disease (PD) by classifying functional near-infrared spectroscopy (fNIRS) studies as PD positive or negative. fNIRS is a non-invasive optical signal modality that conveys the brain's hemodynamic response, specifically changes in blood oxygenation in the cerebral cortex; and its potential as a tool to assist PD detection deserves to be explored since it is non-invasive and cost-effective as opposed to other neuroimaging modalities. Besides the integration of fNIRS and machine learning, a contribution of this work is that various approaches were implemented and tested to find the implementation that achieves the highest performance. All the implementations used a logistic regression model for classification. A set of 792 temporal and spectral features were extracted from each participant's fNIRS study. In the two best performing implementations, an ensemble of feature-ranking techniques was used to select a reduced feature subset, which was subsequently reduced with a genetic algorithm. Achieving optimal detection performance, our approach reached 100 % accuracy, precision, and recall, with an F1 score and area under the curve (AUC) of 1, using 14 features. This significantly advances PD diagnosis, highlighting the potential of integrating fNIRS and machine learning for non-invasive PD detection.","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"763-771"},"PeriodicalIF":3.8,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563090","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