6 research outputs found
Novel NIR-II organic fluorophores for bioimaging beyond 1550 nm
This work was partially supported by grants from NSFC (81773674, 81573383, and 21473041), NSFHP (2017CFA024, 2017CFB711, and 2016ACA126), the Applied Basic Research Program of WMBST (2019020701011429), Tibet Autonomous Region Science and Technology Plan Project Key Project (XZ201901-GB-11), Project First-Class Disciplines Development Supported by Chengdu University of Traditional Chinese Medicine (CZYJC1903), and Health Commission of Hubei Province Scientific Research Project (WJ2019M177 and WJ2019M178).Peer reviewedPublisher PD
The Application of Ethnomedicine in Modulating Megakaryocyte Differentiation and Platelet Counts
Megakaryocytes (MKs), a kind of functional hematopoietic stem cell, form platelets to maintain platelet balance through cell differentiation and maturation. In recent years, the incidence of blood diseases such as thrombocytopenia has increased, but these diseases cannot be fundamentally solved. The platelets produced by MKs can treat thrombocytopenia-associated diseases in the body, and myeloid differentiation induced by MKs has the potential to improve myelosuppression and erythroleukemia. Currently, ethnomedicine is extensively used in the clinical treatment of blood diseases, and the recent literature has reported that many phytomedicines can improve the disease status through MK differentiation. This paper reviewed the effects of botanical drugs on megakaryocytic differentiation covering the period 1994–2022, and information was obtained from PubMed, Web of Science and Google Scholar. In conclusions, we summarized the role and molecular mechanism of many typical botanical drugs in promoting megakaryocyte differentiation in vivo, providing evidence as much as possible for botanical drugs treating thrombocytopenia and other related diseases in the future
Proteomic Analysis and NIR-II Imaging of MCM2 Protein in Hepatocellular Carcinoma
Targeted therapy of hepatocellular
carcinoma (HCC) is essential
for improved therapies. Therefore, identification of key targets specifically
to HCC is an urgent requirement. Herein, an iTRAQ quantitative proteomic
approach was employed to identify differentially expressed proteins
in HCC tumor tissues. Of the upregulated tumor-related proteins, minichromosome
maintenance 2 (MCM2), a DNA replication licensing factor, was one
of the most significantly altered proteins, and its overexpression
was confirmed using tissue microarray. Clinicopathological analysis
of multiple cohorts of HCC patients indicated that overexpression
of MCM2 was validated in 89.8% tumor tissues and strongly correlated
with clinical stage. Furthermore, siRNA-mediated repression of MCM2
expression resulted in significant suppression of the HepG2 cell cycle
and proliferation through the cyclin D-dependent kinases (CDKs) 2/7
pathway. Finally, the first small molecule-based MCM2-targeted NIR-II
probe <b>CH1055-MCM2</b> was concisely generated and subsequently
evaluated in mice bearing HepG2 xenografts. The excellent imaging
properties such as good tumor uptake and high tumor contrast and specificity
were achieved in the small animal models. This analytical strategy
can determine novel accessible targets of HCC useful for imaging and
therapy
Protein Profiling of Active Cysteine Cathepsins in Living Cells Using an Activity-Based Probe Containing a Cell-Penetrating Peptide
Cell-permeable activity-based probes (ABPs) are capable of labeling
target proteins in living cells, thereby providing a powerful tool
for profiling active enzymes in their native environment. In this
study, we describe the synthesis and use of a novel trifunctional
cell-permeable activity-based probe (TCpABP) for proteomic profiling
of active cysteine cathepsins in living cells. We demonstrate that
although TCpABP contains cell-impermeable tags, it was able to enter
living cells efficiently via the delivery of a cell-penetrating peptide.
TCpABP also allowed simultaneous detection and affinity isolation
of labeled proteins with a fluorophore and a biotin motif, respectively.
We optimized the enrichment protocol to minimize contaminants and
identified 7 cathepsins, 2 of which have never been identified using
existing ABPs. We also used a label-free quantification approach to
quantify the relative abundances of active cathepsins and compared
them with their previously published mRNA expression levels. A high
degree of correlation between the mRNA expression levels and protein
relative activities was observed for most of the identified cathepsins
except cathepsin H. The results herein indicate that TCpABP is valuable
for the detection of active cathepsins in living cells and provides
useful guidelines for designing novel cell-permeable ABPs for <i>in vivo</i> labeling and their applications in <i>in vivo</i> proteomics studies
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Proteomics Links Ubiquitin Chain Topology Change to Transcription Factor Activation
A surprising complexity of ubiquitin signaling has emerged with identification of different ubiquitin chain topologies. However, mechanisms of how the diverse ubiquitin codes control biological processes remain poorly understood. Here, we use quantitative whole-proteome mass spectrometry to identify yeast proteins that are regulated by lysine 11 (K11)-linked ubiquitin chains. The entire Met4 pathway, which links cell proliferation with sulfur amino acid metabolism, was significantly affected by K11 chains and selected for mechanistic studies. Previously, we demonstrated that a K48-linked ubiquitin chain represses the transcription factor Met4. Here, we show that efficient Met4 activation requires a K11-linked topology. Mechanistically, our results propose that the K48 chain binds to a topology-selective tandem ubiquitin binding region in Met4 and competes with binding of the basal transcription machinery to the same region. The change to K11-enriched chain architecture releases this competition and permits binding of the basal transcription complex to activate transcription