European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 284, С. 117212 - 117212
Опубликована: Дек. 27, 2024
Язык: Английский
Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 75 - 75
Опубликована: Янв. 10, 2025
Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of tumor microenvironment (TME), leading important advancements toward a much deeper understanding how heterogeneity contributes cancer progression therapeutic resistance. These are able integrate data from molecular genomic, transcriptomic, proteomics, metabolomics studies cells at resolution scale that give rise full cellular complexity TME. Understanding complex sometimes reciprocal relationships among cells, CAFs, immune ECs has led novel insights into their immense functions, which can consequences on behavior. In-depth uncovered evasion mechanisms, including exhaustion T metabolic reprogramming response hypoxia cells. Single-cell also revealed resistance such as stromal cell-secreted factors physical barriers extracellular matrix. Future examining specific pathways targeting approaches reduce TME will likely lead better outcomes with immunotherapies, drug delivery, etc., for treatments. incorporate data, spatial micro-environments, translation personalized therapies. This review emphasizes provide TME, revealing reprogramming, influences. aim guide development targeted therapies, highlighting role diversity shaping behavior treatment outcomes.
Язык: Английский
Процитировано
3
Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown
Опубликована: Янв. 9, 2025
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that target undruggable proteins, enhance selectivity and prevent accumulation through catalytic activity. The unique structure of PROTACs presents challenges in structural identification drug design. Liquid chromatography (LC), combined with mass spectrometry (MS), enhances compound annotation by providing essential retention time (RT) data, especially when MS alone is insufficient. However, predicting RT for remains challenging. To address this, we compiled the PROTAC-RT data set from literature evaluated performance four machine learning algorithms─extreme gradient boosting (XGBoost), random forest (RF), K-nearest neighbor (KNN) support vector machines (SVM)─and a deep model, fully connected neural network (FCNN), using 24 molecular fingerprints descriptors. Through screening combinations fingerprints, descriptors chromatographic condition (CCs), developed an optimized XGBoost model (XGBoost + moe206+Path Charge CCs) achieved R2 0.958 ± 0.027 RMSE 0.934 0.412. After hyperparameter tuning, model's improved to 0.963 0.023, 0.896 0.374. showed strong predictive accuracy under new separation conditions was validated six experimentally determined compounds. SHapley Additive exPlanations (SHAP) not only highlights advantages but also emphasizes importance CCs features, such as bond variability, van der Waals surface area, atomic charge states. combines moe206, path, descriptors, CCs, fast precise method compounds, thus facilitating their annotation.
Язык: Английский
Процитировано
1
Cells, Год журнала: 2025, Номер 14(3), С. 156 - 156
Опубликована: Янв. 21, 2025
Disruptions in uterine tissue function contribute to disorders such as endometriosis, adenomyosis, endometrial cancer, and fibroids, which all significantly impact health fertility. Advances transcriptomics, particularly single-cell RNA sequencing, have revolutionized biological research by revealing the cellular heterogeneity molecular mechanisms underlying disease states. Single-cell sequencing spatial transcriptomics mapped myometrial landscapes, helped identify critical cell types, signaling pathways, phase-specific dynamics. Said transcriptomic technologies also identified stromal immune dysfunctions, fibroblast-to-myofibroblast transitions impaired macrophage activity, drive fibrosis, chronic inflammation, lesion persistence endometriosis. For scRNA-seq uncovered tumor microenvironmental complexities, identifying cancer-associated fibroblast subtypes profiles contributing progression therapeutic resistance. Similarly, studies on adenomyosis highlighted disrupted including Wnt VEGF, novel progenitor populations linked invasion neuroinflammation, while approaches characterized smooth muscle subpopulations elucidating their roles extracellular matrix remodeling pathways like ERK mTOR. Despite challenges scalability reproducibility, may potential applications biomarker discovery, target identification, personalized medicine gynecological disorders.
Язык: Английский
Процитировано
1
European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 279, С. 116904 - 116904
Опубликована: Сен. 24, 2024
Язык: Английский
Процитировано
7
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 772 - 772
Опубликована: Янв. 17, 2025
We previously isolated a cDNA clone for galactosylceramide expression factor 1, which is the rat homologue of hepatocyte-growth-factor-regulated tyrosine kinase substrate (HGS) and induces morphological changes in COS-7 cells, reported that overexpression HGS induced canine kidney epithelial MDCK cells. component endosomal sorting complexes required transport machinery mediates multivesicle body formation. In this study, epithelial–mesenchymal transition caused transformation whereas coiled-coil domain inhibited induction by HGF stimulation. The mouse melanoma B16 cells human colorectal cancer COLO205 promoted characteristic anchorage-independent cell growth ability tumor growth, these suppressed them. oligopeptide OP12-462 constituting are novel inhibitors do not directly destroy but rather inhibit only
Язык: Английский
Процитировано
0
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
RSC Medicinal Chemistry, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
Strong ligand directed degraders stabilize the hydrophobic residue burial between E3 ligase and target protein to be degraded. Weak destabilize ternary complex through multiple mechanisms.
Язык: Английский
Процитировано
0
Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 248 - 248
Опубликована: Фев. 12, 2025
Background: Doxorubicin (DOX) is a very powerful chemotherapy drug. However, its severe toxicity and potential for resistance development limit application. Withania somnifera L. Dunal (WIT) has therapeutic capacities, including anti-inflammatory, antioxidant, anticancer activities. This study investigates the preventative benefits of standardized WIT extract against DOX-induced renal damage in vivo. We also investigate synergistic effects combining DOX to improve efficacy breast cancer cells (MCF7-ADR). Methods: employed an animal model where rats were administered 300 mg/kg/day orally duration 14 days. Rats received injections at dose 5 mg/kg, total 15 mg, on 6th, 8th, 10th Results: Present results revealed that reduced increase levels blood urea creatinine activity kidney injury molecule-1. tissue damage, oxidative stress, pro-inflammatory markers. alleviated nuclear factor erythroid 2-related 2, heme oxygenase-1, sirtuin 1 tissues. modulated factor-κB decreased apoptotic indicators. Furthermore, improves DOX's capacity kill drug-resistant MCF7-ADR by arresting cell cycle promoting apoptosis. Chemical analysis root 34 distinct compounds, alkaloids, withanolides, flavanones, fatty acids. Conclusions: These constituents synergistically contribute WIT's anti-apoptotic properties. In addition, they confirm ability reduce systemic while improving treatment efficacy.
Язык: Английский
Процитировано
0
Molecules, Год журнала: 2025, Номер 30(6), С. 1204 - 1204
Опубликована: Март 7, 2025
Phenanthrenes, which are polycyclic aromatic hydrocarbons comprising three benzene rings, exhibit a diverse range of functions. These compounds utilized in the synthesis resins, plant growth hormones, reducing dyes, tannins and other products. Notably, phenanthrenes possess significant pharmacological properties, including anti-tumor, anti-inflammatory antioxidant activities, offering broad prospects for development, particularly fields medicine health. Interestingly, although aristolochic acid (AA) is potent carcinogen, its lactam analogs can kill cancer cells therapeutic effects against cancer. This provides promising strategy toxicity-effect transformation phenanthrenes. In this paper, we reviewed 137 articles to systematically review anti-tumor potential toxic natural isolated from 19th century present, thus references laying foundation their further research, development utilization.
Язык: Английский
Процитировано
0
Bioanalysis, Год журнала: 2025, Номер unknown, С. 1 - 16
Опубликована: Фев. 3, 2025
Undruggable targets account for roughly 85% of human disease-related and represent a category therapeutic that are difficult to tackle with traditional methods, but their considerable clinical importance. These generally defined by planar functional interfaces the absence efficient ligand-binding pockets, making them unattainable conventional pharmaceutical strategies. The advent oligonucleotide-based proteolysis-targeting chimeras (PROTACs) has instilled renewed optimism in addressing these challenges. PROTACs facilitate targeted degradation undruggable entities, including transcription factors (TFs) RNA-binding proteins (RBPs), via proteasome-dependent mechanisms, thereby presenting novel approaches diseases linked targets. This review offers an in-depth examination recent progress integration PROTAC technology oligonucleotides target traditionally proteins, emphasizing design principles mechanisms action innovative PROTACs.
Язык: Английский
Процитировано
0