Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models.

Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC).

Hypoxia-inducible factor-1α-deficient adipose-tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein-1.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane generally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming 'beige' adipocytes.

Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking functional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation.

TRPV4 modulation affects mitochondrial parameters in adipocytes and its inhibition upregulates lipid accumulation.

Enhanced lipid-droplet formation by adipocytes is a complex process and relevant for obesity. Using knock-out animals, involvement of TRPV4, a thermosensitive ion channel in the obesity has been proposed. However, exact role/s of TRPV4 in adipogenesis and obesity remain unclear and contradictory.

Atom-Efficient Synthesis of Trimethine Cyanines Using Formaldehyde as a Single-Carbon Source.

Herein, we present an innovative and atom-efficient synthesis of trimethine cyanines (Cy3) using formaldehyde (FA) as a single-carbon reagent. The widespread application of Cy3 dyes in bioimaging and genomics/proteomics is often limited by synthetic routes plagued by low atom economy and substantial side-product formation. Through systematic investigation, we have developed a practical and efficient synthetic pathway for both symmetrical and unsymmetrical Cy3 derivatives, significantly minimizing resource utilization.

Reduced dynamicity and increased high-order protein assemblies in dense fibrillar component of the nucleolus under cellular senescence.

Cellular senescence, which is triggered by various stressors, manifests as irreversible cell cycle arrest, resulting in the disruption of multiple nuclear condensates. One of the affected structures is the nucleolus, whose tripartite layout, separated into distinct liquid phases, allows for the stepwise progression of ribosome biogenesis. The dynamic properties of dense fibrillar components, a sub-nucleolar phase, are crucial for mediating pre-rRNA processing.

TRPM8 affects relative "cooling and heating" of subcellular organelles in microglia in a context-dependent manner.

Thermoregulation and thermal homeostasis at the cellular and subcellular organelle level are poorly understood events. In this work, we used BV2, a microglial cell line, and a series of thermo-sensitive subcellular organelle-specific probes to analyze the relative changes in the spatio-temporal temperatures of different subcellular organelles, both qualitatively and quantitatively. These methodologies allowed us to understand the thermal relationship of different subcellular organelles also.

Development of a specific fluorescent probe to detect advanced glycation end products (AGEs).

Advanced glycation end products (AGEs) play a pivotal role in the aging process, regarded as a hallmark of aging. Despite their significance, the absence of adequate monitoring tools has hindered the exploration of the relationship between AGEs and aging. Here, we present a novel AGE-selective probe, AGO, for the first time.

Development of a Mature B Lymphocyte Probe through Gating-Oriented Live-Cell Distinction (GOLD) and Selective Imaging of Topical Spleen.

B lymphocytes play a pivotal role in the adaptive immune system by facilitating antibody production. Young B cell progenitors originate in the bone marrow and migrate to the spleen for antigen-dependent maturation, leading to the development of diverse B cell subtypes. Thus, tracking B cell trajectories through cell type distinction is essential for an appropriate checkpoint assessment.

Novel Fluorescent Strategy for Discriminating T and B Lymphocytes Using Transport System.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways.

Discovery of Live Cell Selective Fluorescent Probes and Elucidation of Their Mechanisms: Case Study of B Cell Selective Probe CDgB.

The development of small-molecule fluorescent probes for specific immune cell identification offers an economical alternative to expensive antibodies. Moreover, it enables the identification of live target cells and provides insights into the distinct properties of cells, leveraging their specific staining mechanisms. This chapter presents a comprehensive elucidation of the methodology employed for screening fluorescent compounds using flow cytometry measurements.

The Effect of 3-Dimensional-Printed Sequential Dual Drug-Releasing Patch on the Capsule Formation Around the Silicone Implant in a Rat Model.

Background: Implant-based breast reconstruction is associated with increased risk of early infection and late-stage capsular contracture.

Objectives: We evaluated the feasibility of a dual drug-releasing patch that enabled the controlled delivery of antibiotics and immunosuppressants in a temporally and spatially appropriate manner to the implant site.

Methods: The efficacy of a dual drug-releasing patch, which was 3-dimensional-printed (3D-printed) with tissue-derived biomaterial ink, was evaluated in rats with silicone implants.

Chronological development of functional fluorophores for bio-imaging.

Functional fluorophores represent an emerging research field, distinguished by their diverse applications, especially in sensing and cellular imaging. After the discovery of quinine sulfate and subsequent elucidation of the fluorescence mechanism by Sir George Stokes, research in the field of fluorescence gained momentum. Over the past few decades, advancements in sophisticated instruments, including super-resolution microscopy, have further promoted cellular imaging using traditional fluorophores.

Mitochondrial temperature homeostasis resists external metabolic stresses.

Based on studies with a fluorescent reporter dye, Mito Thermo Yellow (MTY), and the genetically encoded gTEMP ratiometric fluorescent temperature indicator targeted to mitochondria, the temperature of active mitochondria in four mammalian and one insect cell line was estimated to be up to 15°C above that of the external environment to which the cells were exposed. High mitochondrial temperature was maintained in the face of a variety of metabolic stresses, including substrate starvation or modification, decreased ATP demand due to inhibition of cytosolic protein synthesis, inhibition of the mitochondrial adenine nucleotide transporter and, if an auxiliary pathway for electron transfer was available via the alternative oxidase, even respiratory poisons acting downstream of oxidative phosphorylation (OXPHOS) complex I. We propose that the high temperature of active mitochondria is an inescapable consequence of the biochemistry of OXPHOS and is homeostatically maintained as a primary feature of mitochondrial metabolism.

NeuM: A Neuron-Selective Probe Incorporates into Live Neuronal Membranes via Enhanced Clathrin-Mediated Endocytosis in Primary Neurons.

The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined.

Distinct chemical environments in biomolecular condensates.

Diverse mechanisms have been described for selective enrichment of biomolecules in membrane-bound organelles, but less is known about mechanisms by which molecules are selectively incorporated into biomolecular assemblies such as condensates that lack surrounding membranes. The chemical environments within condensates may differ from those outside these bodies, and if these differed among various types of condensate, then the different solvation environments would provide a mechanism for selective distribution among these intracellular bodies. Here we use small molecule probes to show that different condensates have distinct chemical solvating properties and that selective partitioning of probes in condensates can be predicted with deep learning approaches.

The Lysosomal Calcium Channel TRPML1 Maintains Mitochondrial Fitness in NK Cells through Interorganelle Cross-Talk.

Cytotoxic lymphocytes eliminate cancer cells through the release of lytic granules, a specialized form of secretory lysosomes. This compartment is part of the pleomorphic endolysosomal system and is distinguished by its highly dynamic Ca2+ signaling machinery. Several transient receptor potential (TRP) calcium channels play essential roles in endolysosomal Ca2+ signaling and ensure the proper function of these organelles.

Development of Iodinated Indocyanine Green Analogs as a Strategy for Targeted Therapy of Liver Cancer.

Liver cancer is one of the leading causes of cancer-related deaths, with a significant increase in incidence worldwide. Novel therapies are needed to address this unmet clinical need. Indocyanine green (ICG) is a broadly used fluorescence-guided surgery (FGS) agent for liver tumor resection and has significant potential for conversion to a targeted therapy.

Improved tropoelastin synthesis in the skin by codon optimization and nucleotide modification of tropoelastin-encoding synthetic mRNA.

Loss of elastin due to aging, disease, or injury can lead to impaired tissue function. In this study, tropoelastin (TE) synthesis is investigated and using different TE-encoding synthetic mRNA variants after codon optimization and nucleotide modification. Codon optimization shows a strong effect on protein synthesis without affecting cell viability , whereas nucleotide modifications strongly modulate translation and reduce cell toxicity.

Menthol causes mitochondrial Ca-influx, affects structure-function relationship and cools mitochondria.

Menthol is a small bioactive compound able to cause several physiological changes and has multiple molecular targets. Therefore, cellular response against menthol is complex, and still poorly understood. In this work, we used a human osteosarcoma cell line (Saos-2) and analysed the effect of menthol, especially in terms of cellular, subcellular and molecular aspects.

Visualization of Metastatic Lung Cancer with TiNIR.

The development of efficient biomarkers and probes for monitoring and treating cancer, specifically metastatic cancer, is a critical research area that can have a significant impact on both patient outcomes and drug discovery. In this context, TiNIR has been developed to detect tumor-initiating cells (TICs), with heme oxygenase 2 (HO2) as a promising therapeutic biomarker for tumor-initiating cells. In this study, TiNIR has demonstrated its effectiveness as an metastatic lung cancer tracker, highlighting its potential as a valuable tool in cancer research and therapy.

Magnetically Enhanced Intracellular Uptake of Superparamagnetic Iron Oxide Nanoparticles for Antitumor Therapy.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely employed in biomedical fields, including targeted delivery of antitumor therapy. Conventional magnetic tumor targeting has used simple static magnetic fields (SMFs), which cause SPIONs to linearly aggregate into a long chain-like shape. Such agglomeration greatly hinders the intracellular targeting of SPIONs into tumors, thus reducing the therapeutic efficacy.

NMN sensor cocktail: selective sensing of nicotinamide mononucleotide over citric acid.

The fluorescent probe pair, NBD-B2 and Styryl-51F, selectively detects NMN over citric acid. NBD-B2 exhibits increased fluorescence, while Styryl-51F shows decreased fluorescence upon NMN addition. Their ratiometric fluorescence change enables highly sensitive and wide-range detection of NMN, effectively distinguishing it not only from citric acid but also other NAD boosters.