ABSTRACT
Endogenous hypochlorous acid (HOCl) is one of the most important reactive oxygen species (ROS) and acts as a distinct biomarker that is involved in various inflammatory responses including rheumatoid arthritis (RA). Therefore, it's crucial to develop an efficient method for the tracking and analysis of HOCl levels in vivo. Natural products continue to be compounds of interest, because they not only offer diverse and specific molecular scaffolds but also provide invaluable sources for new drug discovery. Herein, we firstly demonstrated harmaline (HML), a natural alkaloid mainly found in Peganum harmala L, could be acted as a novel fluorescent probe for HOCl with exceptional precision and responsiveness. Remarkably, this probe not only specifically tracked HOCl levels in cells and inflammatory RA mouse models, but also exhibited effective anti-inflammatory effects on RAW264.7 cells and anti-proliferative effects on fibroblast-like synoviocytes. Furthermore, HML has the potential to alleviate LPS-induced inflammation by inhibiting the NF-κB signaling pathway. This study represents the first example of a natural product that can simultaneously act as a fluorescent probe for specific ROS and a promising therapeutic candidate for a specific disease, which will undoubtedly extend the application of fluorophore-rich natural products.
ABSTRACT
Exogenous sulfur dioxide (SO2) and its derivatives (SO32-/HSO3-) have been extensively utilized in food preservation and endogenous SO2 is recognized as a significant gaseous signaling molecule that can mediate various physiological processes. Overproduction and/or extensive intake of these species can trigger allergic reactions and even tissue damage. Therefore, it is highly desirable to monitor SO2 and its derivatives effectively and quantitatively both in vitro and in vivo. Herein, a new mitochondria-targeted fluorescent probe (PIB) had been constructed, which could ratiometrically recognize SO2 and its derivatives with excellent sensitivity (DL = 15.9 nM) and a fast response time (200 s). The obtained high selectivity and good adaptability of this SO2-specific probe in a wide pH range (6.5-10.0) allowed for quantitatively tracking of SO2 and its derivatives in real food samples (granulated sugar, crystal sugar, and white wine). In addition, PIB could locate at mitochondrion and was capable of imaging exogenous/endogenous SO2 in the cells and zebrafish. In particular, our findings represented one of the rare examples that have demonstrated endogenous SO2 is closely related with the apoptosis of cells. Importantly, probe PIB was successfully employed for in situ metabolic localization in mouse organs, implying the potential applications of our probe in further exploration on SO2-releated pathological and physiological processes.
Subject(s)
Fluorescent Dyes , Sulfur Dioxide , Humans , Animals , Mice , Sulfur Dioxide/analysis , Sulfur Dioxide/chemistry , Fluorescent Dyes/chemistry , Zebrafish , Food Analysis , HeLa Cells , SugarsABSTRACT
Cysteine (Cys), one of essential small-molecule-based biothiols in the human body, contributes to the regulation of redox reactions and is closely associated with many physiological and pathological metabolic processes. Herein, a novel fluorescent probe, hydroxyphenyl-conjugated benzothiazole (HBT-Cys) capable of detecting Cys was constructed, where acrylate served as the recognition group and hydroxyphenyl-linked benzothiazole acted as the fluorophore. The fluorescence of the probe was negligible in the absence of Cys, and an intense blue fluorescence was observed upon addition of Cys. The Cys-sensing mechanism could be ascribed to the Cys-involved hydrolysis reaction with acrylate, leading to light up the emission at 430 nm with about 80-fold enhancement. In addition, HBT-Cys exhibited a fast response time, remarkable selectivity and low detection limit. HBT-Cys also worked well in real-time monitoring of Cys in three different food samples (wolfberry, hawthorn, and red dates). Importantly, our probe had an excellent lysosomes-targeted ability, which was successfully employed to real-time visualize the fluctuation of both exogenous and endogenous Cys in living cells and zebrafish under lipopolysaccharide (LPS)-induced oxidative stress. Hopefully, the work shown here provides a potent candidate for the real-time tracking of Cys fluctuations in various biological samples.
Subject(s)
Cysteine , Fluorescent Dyes , Animals , Humans , Fluorescent Dyes/metabolism , Cysteine/metabolism , Lipopolysaccharides/pharmacology , HeLa Cells , Zebrafish , Lysosomes/metabolism , Oxidative Stress , Acrylates , Benzothiazoles/metabolism , Glutathione/metabolismABSTRACT
Fluorescence microscopy has proven to be a crucial powerful tool to specifically visualize cellular organelles. In-depth visualization of the structure of mitochondria in living cells is of great value to better understand their function. Herein, based on our experience in construction of fluorescent difluoroboronate anchored acylhydrazones (BOAHY) chromophores, we rationally designed a novel monoboron complex with a connected triphenylphosphonium moiety, and evaluated its spectroscopic properties, cytotoxicity and intracellular localization. Owing to the positive charge on our fluorescent dye, the molecule had an excellent mitochondria-targeting ability (Pearson's correlation is 0.86).To the best of our knowledge, this is the first example of a BOAHY dye which has been applied as an efficient tracker to target mitochondria in living cells.
Subject(s)
Fluorescent Dyes , Mitochondria , Mitochondria/chemistry , Fluorescent Dyes/chemistryABSTRACT
Liposarcoma was mainly occurring in the lower extremities and deep retroperitoneal soft tissues, but rarely occurred in the thoracic cavity. Most cases were reported in the literature, and most of them were middle-aged and elderly people. It was even more rare in adolescents with tumors occupying the entire thoracic cavity. Recently, one case of myxomatous liposarcoma was admitted and treated in our hospital. This paper reports this case and discusses the diagnostic method, pathological type and treatment of giant liposarcoma in the chest, in order to provide a reference for the clinical diagnosis and treatment of this rare tumor.
ABSTRACT
OBJECTIVE: Using a genotying method which is accurate and rapid to study the molecular epidemiology of EsBLs-producing Escherichia coli in nosocomial infection. METHODS: After an analysis of clinical information to ascertain nosocomial infection, EsBLs were detected by phenotype confirmation test and pulsed-field gel electrophoresis (PFGE). RESULTS: Three EsBLs-producing strains in ICU were verified as epidemiological-related because their dice coefficient index was higher than 95%. The others were verified as non-epidemiological-related since their different lanes were more than 6. CONCLUSION: PFGE is a perfect molecular typing method to study epidemiolgy and analyze homology.