Identification and Characterization of Metastasis-Initiating Cells in ESCC in a Multi-Timepoint Pulmonary Metastasis Mouse Model.

Metastasis is the biggest obstacle to esophageal squamous cell carcinoma (ESCC) treatment. Single-cell RNA sequencing analyses are applied to investigate lung metastatic ESCC cells isolated from pulmonary metastasis mouse model at multiple timepoints to characterize early metastatic microenvironment. A small population of parental KYSE30 cell line (Cluster S) resembling metastasis-initiating cells (MICs) is identified because they survive and colonize at lung metastatic sites. Differential expression profile comparisons between Cluster S and other subpopulations identified a panel of 7 metastasis-initiating signature genes (MIS), including CD44 and TACSTD2, to represent MICs in ESCC. Functional studies demonstrated MICs (CD44high) exhibited significantly enhanced cell survival (resistances to oxidative stress and apoptosis), migration, invasion, stemness, and in vivo lung metastasis capabilities, while bioinformatics analyses revealed enhanced organ development, stress responses, and neuron development, potentially remodel early metastasis microenvironment. Meanwhile, early metastasizing cells demonstrate quasi-epithelial-mesenchymal phenotype to support both invasion and anchorage. Multiplex immunohistochemistry (mIHC) staining of 4 MISs (CD44, S100A14, RHOD, and TACSTD2) in ESCC clinical samples demonstrated differential MIS expression scores (dMISs) predict lymph node metastasis, overall survival, and risk of carcinothrombosis.

Regular Use of Aspirin and Statins Reduces the Risk of Cancer in Individuals with Systemic Inflammatory Diseases.

Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SID), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy. SIGNIFICANCE: Individuals with systemic inflammatory diseases derive chemoprotective benefits from aspirin and statins, providing a precision cancer prevention approach to address the personal and public challenges posed by cancer.

Meet the Medicines-A Crowdsourced Approach to Collecting and Communicating Information about Essential Medicines Online.

The World Health Organization (WHO) maintains a list of medicines and medical devices, essential medicines, that should be available to everyone, to form a functioning healthcare system. Yet, many of these medicines remain out of reach for people around the world. One significant barrier to improving the accessibility of essential medicines is a paucity of information about both the extent and causes of this problem. E$$ENTIAL MEDICINE$ (E$$) is a citizen science project designed to investigate this deficit of information by recruiting members of the public to find, validate, compile and share information on essential medicines through an open, online database. Herein, we report an approach to crowdsourcing both the collection of information on the accessibility of essential medicines and the subsequent communication of these findings to diverse audiences. The Meet the Medicines initiative encourages members of the public to share information from the E$$ database, in a short video format appropriate for social media. This communication details the design and implementation of our crowdsourced approach and strategies for recruiting and supporting participants. We discuss data on participant engagement, consider the benefits and challenges of this approach and suggest ways to promote crowdsourcing practices for social and scientific good.

Photochemical Mechanisms of Fluorophores Employed in Single-Molecule Localization Microscopy.

Decoding cellular processes requires visualization of the spatial distribution and dynamic interactions of biomolecules. It is therefore not surprising that innovations in imaging technologies have facilitated advances in biomedical research. The advent of super-resolution imaging technologies has empowered biomedical researchers with the ability to answer long-standing questions about cellular processes at an entirely new level. Fluorescent probes greatly enhance the specificity and resolution of super-resolution imaging experiments. Here, we introduce key super-resolution imaging technologies, with a brief discussion on single-molecule localization microscopy (SMLM). We evaluate the chemistry and photochemical mechanisms of fluorescent probes employed in SMLM. This Review provides guidance on the identification and adoption of fluorescent probes in single molecule localization microscopy to inspire the design of next-generation fluorescent probes amenable to single-molecule imaging.

Strategies for organelle targeting of fluorescent probes.

Fluorescent tools have emerged as an important tool for studying the distinct chemical microenvironments of organelles, due to their high specificity and ability to be used in non-destructive, live cellular studies. These tools fall largely in two categories: exogenous fluorescent dyes, or endogenous labels such as genetically encoded fluorescent proteins. In both cases, the probe must be targeted to the organelle of interest. To date, many organelle-targeted fluorescent tools have been reported and used to uncover new information about processes that underpin health and disease. However, the majority of these tools only apply a handful of targeting groups, and less-studied organelles have few robust targeting strategies. While the development of new, robust strategies is difficult, it is essential to develop such strategies to allow for the development of new tools and broadening the effective study of organelles. This review aims to provide a comprehensive overview of the major targeting strategies for both endogenous and exogenous fluorescent cargo, outlining the specific challenges for targeting each organelle type and as well as new developments in the field.

A Bimodal Fluorescence-Raman Probe for Cellular Imaging.

Biochemical changes in specific organelles underpin cellular function, and studying these changes is crucial to understand health and disease. Fluorescent probes have become important biosensing and imaging tools as they can be targeted to specific organelles and can detect changes in their chemical environment. However, the sensing capacity of fluorescent probes is highly specific and is often limited to a single analyte of interest. A novel approach to imaging organelles is to combine fluorescent sensors with vibrational spectroscopic imaging techniques; the latter provides a comprehensive map of the relative biochemical distributions throughout the cell to gain a more complete picture of the biochemistry of organelles. We have developed NpCN1, a bimodal fluorescence-Raman probe targeted to the lipid droplets, incorporating a nitrile as a Raman tag. NpCN1 was successfully used to image lipid droplets in 3T3-L1 cells in both fluorescence and Raman modalities, reporting on the chemical composition and distribution of the lipid droplets in the cells.