Basic Research in Cardiology, Год журнала: 2023, Номер 118(1)
Опубликована: Фев. 7, 2023
Язык: Английский
Nature Cancer, Год журнала: 2023, Номер 4(4), С. 454 - 467
Опубликована: Март 23, 2023
Язык: Английский
Процитировано
52
Nature Methods, Год журнала: 2024, Номер 21(3), С. 531 - 540
Опубликована: Янв. 26, 2024
Язык: Английский
Процитировано
52
Nature Medicine, Год журнала: 2024, Номер 30(3), С. 699 - 707
Опубликована: Фев. 19, 2024
Abstract Regorafenib has anti-tumor activity in patients with unresectable hepatocellular carcinoma (uHCC) potential immunomodulatory effects, suggesting that its combination immune checkpoint inhibitor may have clinically meaningful benefits uHCC. The multicenter, single-arm, phase 2 RENOBATE trial tested regorafenib–nivolumab as front-line treatment for Forty-two received nivolumab 480 mg every 4 weeks and regorafenib 80 daily (3-weeks-on/1-week-off schedule). primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria Solid Tumors (RECIST) version 1.1. secondary endpoints included safety, progression-free survival (PFS) overall (OS). ORR RECIST 1.1 31.0%, meeting endpoint. most common adverse events were palmar-plantar erythrodysesthesia syndrome (38.1%), alopecia (26.2%) skin rash (23.8%). Median PFS 7.38 months. 1-year OS 80.5%, median not reached. Exploratory single-cell RNA sequencing analyses of peripheral blood mononuclear cells showed long-term responders exhibited T cell receptor repertoire diversification, enrichment genes representing immunotherapy responsiveness MKI67 + proliferating CD8 a higher probability M1-directed monocyte polarization. Our data support further clinical development uHCC provide preliminary insights on biomarkers response. ClinicalTrials.gov identifier: NCT04310709 .
Язык: Английский
Процитировано
25
Cell Metabolism, Год журнала: 2024, Номер 36(1), С. 90 - 102.e7
Опубликована: Янв. 1, 2024
Interactions between lineage-determining and activity-dependent transcription factors determine single-cell identity function within multicellular tissues through incompletely known mechanisms. By assembling a atlas of chromatin state human islets, we identified β cell subtypes governed by either high or low activity the factor pancreatic duodenal homeobox-1 (PDX1). cells with reduced PDX1 displayed increased accessibility at latent nuclear κB (NF-κB) enhancers. Pdx1 hypomorphic mice exhibited de-repression NF-κB impaired glucose tolerance night. Three-dimensional analyses in tandem immunoprecipitation (ChIP) sequencing revealed that silences circadian inflammatory enhancers long-range contacts involving SIN3A. Conversely, Bmal1 ablation disrupted genome-wide DNA binding. Finally, antagonizing interleukin (IL)-1β receptor, an target, improved insulin secretion islets. Our studies reveal functional single defined gradient identify as target for insulinotropic therapy.
Язык: Английский
Процитировано
19
Acta Biochimica Polonica, Год журнала: 2025, Номер 72
Опубликована: Фев. 5, 2025
In recent years, significant advancements in biochemistry, materials science, engineering, and computer-aided testing have driven the development of high-throughput tools for profiling genetic information. Single-cell RNA sequencing (scRNA-seq) technologies established themselves as key dissecting sequences at level single cells. These reveal cellular diversity allow exploration cell states transformations with exceptional resolution. Unlike bulk sequencing, which provides population-averaged data, scRNA-seq can detect subtypes or gene expression variations that would otherwise be overlooked. However, a limitation is its inability to preserve spatial information about transcriptome, process requires tissue dissociation isolation. Spatial transcriptomics pivotal advancement medical biotechnology, facilitating identification molecules such their original context within sections single-cell level. This capability offers substantial advantage over traditional techniques. valuable insights into wide range biomedical fields, including neurology, embryology, cancer research, immunology, histology. review highlights approaches, technological developments, associated challenges, various techniques data analysis, applications disciplines microbiology, neuroscience, reproductive biology, immunology. It critical role characterizing dynamic nature individual
Язык: Английский
Процитировано
6
Cancers, Год журнала: 2021, Номер 13(22), С. 5856 - 5856
Опубликована: Ноя. 22, 2021
Several clinicopathological features of clear cell renal carcinomas (ccRCC) contribute to make an “atypical” cancer, including resistance chemotherapy, sensitivity anti-angiogenesis therapy and ICIs despite a low mutational burden, CD8+ T infiltration being the predictor for poor prognosis–normally is good prognostic factor in cancer patients. These have brought researchers investigate molecular immunological mechanisms that lead increased infiltrates relatively burdens, as well decipher immune landscape leads better response ICIs. In present study, we summarize past ongoing pivotal clinical trials immunotherapies ccRCC, emphasizing potential cellular success or failure ICI therapy. Single-cell analysis ccRCC has provided more thorough detailed understanding tumor microenvironment facilitated discovery biomarkers from tumor-infiltrating cells. We herein will focus on discussion some major cells, cells tumor-associated macrophages (TAM) ccRCC. further provide perspectives using derived these types potentially improve rate
Язык: Английский
Процитировано
59
Science Advances, Год журнала: 2022, Номер 8(48)
Опубликована: Ноя. 30, 2022
Recent advances in single-cell sequencing technologies have provided unprecedented opportunities to measure the gene expression profile and RNA velocity of individual cells. However, modeling transcriptional dynamics is computationally challenging because high-dimensional, sparse nature measurements nonlinear regulatory relationships. Here, we present DeepVelo , a neural network–based ordinary differential equation that can model complex transcriptome by describing continuous-time changes within We apply public datasets from different platforms (i) formulate on time scales, (ii) instability cell states, (iii) identify developmental driver genes via perturbation analysis. Benchmarking against state-of-the-art methods shows learn more accurate representation field. Furthermore, our studies reveal dynamical systems could exhibit chaotic properties. In summary, allows data-driven discoveries equations delineate dynamics.
Язык: Английский
Процитировано
59
Translational Oncology, Год журнала: 2022, Номер 27, С. 101556 - 101556
Опубликована: Окт. 19, 2022
The field of single-cell omics is rapidly progressing. Although DNA and RNA sequencing-based methods have dominated the to date, global proteome profiling has also entered main stage. Single-cell proteomics was facilitated by advancements in different aspects mass spectrometry (MS)-based proteomics, such as instrument design, sample preparation, chromatography ion mobility. (scp-MS) moved beyond being a mere technical development, now able deliver actual biological application been successfully applied characterize cell states. Here, we review some key developments scp-MS, provide background field, discuss various available foresee possible future directions.
Язык: Английский
Процитировано
53
Nature Communications, Год журнала: 2022, Номер 13(1)
Опубликована: Дек. 10, 2022
Spatially resolved transcriptomics provides the opportunity to investigate gene expression profiles and spatial context of cells in naive state, but at low transcript detection sensitivity or with limited throughput. Comprehensive annotating cell types spatially understand biological processes single level remains challenging. Here we propose Spatial-ID, a supervision-based typing method, that combines existing knowledge reference single-cell RNA-seq data information data. We present series benchmarking analyses on publicly available datasets, demonstrate superiority Spatial-ID compared state-of-the-art methods. Besides, apply self-collected mouse brain hemisphere dataset measured by Stereo-seq, shows scalability three-dimensional large field tissues subcellular resolution.
Язык: Английский
Процитировано
52
Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10
Опубликована: Окт. 24, 2022
Neurodegenerative diseases affect millions of people worldwide and there are currently no cures. Two types common neurodegenerative Alzheimer’s (AD) Parkinson’s disease (PD). Single-cell single-nuclei RNA sequencing (scRNA-seq snRNA-seq) have become powerful tools to elucidate the inherent complexity dynamics central nervous system at cellular resolution. This technology has allowed identification cell states, providing new insights into susceptibilities molecular mechanisms underlying conditions. Exciting research using high throughput scRNA-seq snRNA-seq technologies study AD PD is emerging. Herein we review recent progress in understanding these state-of-the-art technologies. We discuss fundamental principles implications single-cell human brain. Moreover, some examples computational analytical required interpret extensive amount data generated from assays. conclude by highlighting challenges limitations application PD.
Язык: Английский
Процитировано
41