Expert Systems with Applications, Год журнала: 2024, Номер unknown, С. 125772 - 125772
Опубликована: Ноя. 1, 2024
Язык: Английский
Science Advances, Год журнала: 2024, Номер 10(17)
Опубликована: Апрель 24, 2024
Critical aspects of physiology and cell function exhibit self-sustained ~24-hour variations termed circadian rhythms. In the liver, rhythms play fundamental roles in maintaining organ homeostasis. Here, we established characterized an vitro liver experimental system which primary human hepatocytes display oscillations. By generating gene expression profiles these over time, demonstrated that their transcriptional state is dynamic across 24 hours identified a set cycling genes with functions related to inflammation, drug metabolism, energy We designed tested treatment protocol minimize atorvastatin- acetaminophen-induced hepatotoxicity. Last, documented circadian-dependent induction pro-inflammatory cytokines when triggered by LPS, IFN-β, or
Язык: Английский
Процитировано
16
Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104632 - 104632
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
1
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Апрель 24, 2024
Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role development and progression of cancer significantly influencing activity cellular function. This insight has led to novel class therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, acetyltransferase methyltransferase aim modulate curb growth uniquely landscape cells. Ongoing research clinical trials are rigorously evaluating efficacy these particularly their ability improve outcomes when used combination with other treatments. Such therapies may more effectively target potentially overcome challenge drug resistance, significant hurdle therapy. Additionally, importance nutrition, inflammation control, circadian rhythm regulation modulating responses been increasingly recognized, highlighting critical modifiers thereby effectiveness pharmacological interventions patient outcomes. drugs represent paradigm shift treatment, offering targeted that promise precise approach treating wide spectrum tumors, fewer side effects compared traditional chemotherapy. progress marks step towards personalized interventions, leveraging unique profiles individual tumors optimize treatment strategies.
Язык: Английский
Процитировано
8
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Май 2, 2024
Introduction: Gastric cancer is one of the most prevalent types worldwide. The World Health Organization (WHO), International Agency for Research on Cancer (IARC), and Global Statistics (GLOBOCAN) reported an age standardized global incidence rate 9.2 per 100,000 individuals gastric in 2022, with a mortality 6.1. Despite considerable progress precision oncology through efforts international consortia, understanding genomic features their influence effectiveness anti-cancer treatments across diverse ethnic groups remains essential. Methods: Our study aimed to address this need by conducting integrated silico analyses identify actionable alterations driver genes, assess impact using deleteriousness scores, determine allele frequencies nine populations: European Finnish, non-Finnish, Latino, East Asian, South African, Middle Eastern, Ashkenazi Jewish, Amish. Furthermore, our goal was prioritize targeted therapeutic strategies based pharmacogenomics clinical guidelines, drug prescriptions, trial data. Results: comprehensive analysis examined 275,634 variants within 60 genes from 730,947 exome sequences 76,215 whole-genome unrelated individuals, identifying 13,542 annotated predicted oncogenic variants. We prioritized deleterious subsequent testing. Additionally, we discovered ARID1A, ATM, BCOR, ERBB2, ERBB3, CDKN2A, KIT, PIK3CA, PTEN, NTRK3, TP53 , CDKN2A that could enhance efficacy therapies, as suggested prescription analyses, reviews current evaluations phase III IV trials targeting proteins. Discussion: These findings underline urgency consolidating devise effective prevention measures, invest profiling underrepresented populations, ensure inclusion minorities future research developed countries.
Язык: Английский
Процитировано
5
Scientific Reports, Год журнала: 2024, Номер 14(1)
Опубликована: Авг. 21, 2024
The druggable proteome refers to proteins that can bind small molecules with appropriate chemical affinity, inducing a favorable clinical response. Predicting through screening and in silico modeling is imperative for drug design. To contribute this field, we developed an accurate predictive classifier cancer-driving using amino acid composition descriptors of protein sequences 13 machine learning linear non-linear classifiers. optimal was achieved the support vector method, utilizing 200 tri-amino descriptors. high performance model evident from area under receiver operating characteristics (AUROC) 0.975 ± 0.003 accuracy 0.929 0.006 (threefold cross-validation). prediction enhanced multi-omics approaches, including target-disease evidence score, shortest pathways cancer hallmarks, structure-based ligandability assessment, unfavorable prognostic analysis, oncogenic variome. Additionally, performed repurposing analysis identify drugs highest affinity capable targeting best predicted proteins. As result, identified 79 key ligandability, 23 them demonstrated significance across 16 TCGA PanCancer types: CDKN2A, BCL10, ACVR1, CASP8, JAG1, TSC1, NBN, PREX2, PPP2R1A, DNM2, VAV1, ASXL1, TPR, HRAS, BUB1B, ATG7, MARK3, SETD2, CCNE1, MUTYH, CDKN2C, RB1, SMARCA4. Moreover, prioritized 11 clinically relevant these This strategy effectively predicts prioritizes biomarkers, therapeutic targets, in-depth studies trials. Scripts are available at https://github.com/muntisa/machine-learning-for-druggable-proteins .
Язык: Английский
Процитировано
5
Journal of Advanced Research, Год журнала: 2024, Номер unknown
Опубликована: Апрель 1, 2024
The treatment of metabolic system, cardiovascular and nervous system diseases remains to be explored. In the internal environment organisms, metabolism substances such as carbohydrates, lipids proteins (including biohormones enzymes) exhibit a certain circadian rhythm maintain energy supply material cycle needed for normal activities organisms. As key factor health can disrupted by pathological conditions, this disruption accelerates progression results in vicious cycle. current treatments targeting have limitations, identification safer more effective regulators is needed. To systematically assess possibility using biological clock natural product target disease intervention, work reviews range evidence on potential effectiveness products protect against system. This manuscript focuses how restore function affecting amplitude expression factors, sleep/wake cycles structure gut microbiota. proposes that rhythm, which regulated rhythm-related factors cycle, crucial new slowing through use products. provides reference molecular modeling perspective time-targeted action drugs.
Язык: Английский
Процитировано
4
Biomedicines, Год журнала: 2024, Номер 12(9), С. 1961 - 1961
Опубликована: Авг. 29, 2024
Circadian rhythms are endogenous behavioral or physiological cycles that driven by a daily biological clock persists in the absence of geophysical environmental temporal cues. rhythm-related genes code for proteins rise and fall rhythmic patterns driving biochemical signals processes from metabolism to physiology behavior. Clock have pivotal role liver homeostasis, their disturbances implicated various disease processes. Encoded play critical roles initiation progression metabolic dysfunction-associated steatohepatitis (MASH) hepatocellular carcinoma (HCC) may become diagnostic markers as well therapeutic targets. Understanding molecular mechanisms underlying circadian will aid interventions broader clinical applications. The present review provides an overview liver’s rhythm health disease, emphasizing MASH oncogenic associations lead HCC.
Язык: Английский
Процитировано
3
European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177290 - 177290
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Biological Rhythm Research, Год журнала: 2025, Номер unknown, С. 1 - 22
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Апрель 14, 2025
Introduction Thyroid cancer, a prevalent endocrine malignancy, has an age-standardized incidence rate of 9.1 per 100,000 people and mortality 0.44 as 2024. Despite significant advances in precision oncology driven by large-scale international consortia, gaps persist understanding the genomic landscape thyroid cancer its impact on therapeutic efficacy across diverse populations. Methods To address this gap, we performed comprehensive data mining silico analyses to identify pathogenic variants driver genes, calculate allele frequencies, assess deleteriousness scores global populations, including African, Amish, Ashkenazi Jewish, East South Asian, Finnish non-Finnish European, Latino, Middle Eastern groups. Additionally, pharmacogenomic profiling, drug prescription, clinical trial were analyzed prioritize targeted strategies. Results Our analysis examined 56,622 40 cancer-driver genes 76,156 human genomes, identifying 5,001 known predicted oncogenic variants. Enrichment revealed critical pathways such MAPK, PI3K-AKT-mTOR, p53 signaling, underscoring their roles pathogenesis. High-throughput validation strategies confirmed actionable alterations RET, BRAF, NRAS, KRAS, EPHA7. Ligandability assessments identified these proteins promising targets. Furthermore, our findings highlight potential inhibitors, vandetanib, dabrafenib, selumetinib, for improving treatment outcomes. Discussion This study underscores significance integrating insights with disparities treatment. The identification population-specific targets provides foundation advancing oncology. Future efforts should focus underrepresented developing prevention strategies, fostering collaboration ensure equitable access testing innovative therapies. These initiatives have transform care align broader goals personalized medicine.
Язык: Английский
Процитировано
0