A near infrared fluorescent probe for rapid sensing of peroxynitrite in living cells and breast cancer mice.

Peroxynitrite (ONOO-) plays an essential role in numerous physiological and pathological processes owing to its strong oxidation and nitrification. Many studies have shown that ONOO- abnormalities are associated with inflammatory diseases, even cancer, such as arthritis, hepatitis, pneumonia, and breast cancer. Thus, developing a trustworthy technology to monitor ONOO- levels is critical in inflammatory or cancer illnesses. Herein, an ultrafast near-infrared (NIR) fluorescent probe (Cy-OH-ONOO) is proposed to detect ONOO- within 30 s. The probe's borate moiety is oxidized and separated from Cy-OH-ONOO, releasing a NIR fluorescence signal after interacting with ONOO- under physiological circumstances. In addition, the probe displays good selectivity and sensitivity towards ONOO- compared to other related biological species. Moreover, it is applied to the image and detects the level fluctuation of ONOO- in living cells and breast cancer mice based on excellent features with high biocompatibility and low toxicity of the developed probe. Therefore, Cy-OH-ONOO could serve as a powerful imaging tool to understand the correlation of ONOO- with inflammatory or breast cancer pathophysiological processes and to assess ONOO- levels in cellular oxidative stress.

A Two-Photon Fluorescent Probe for the Visual Detection of Peroxynitrite in Living Cells and Zebrafish.

Peroxynitrite (ONOO-), as an important reactive oxygen species (ROS), holds great potential to react with a variety of biologically active substances, leading to the occurrence of various diseases such as cancer and neurodegenerative diseases. In this work, we developed a novel mitochondria-localized fluorescent probe, HDBT-ONOO-, which was designed as a mitochondria-targeting two-photon fluorescence probe based on 1,8-naphthylimide fluorophore and the reactive group of 4-(bromomethyl)-benzene boronic acid pinacol ester. More importantly, the probe exhibited good biocompatibility, sensitivity, and selectivity, enabling its successful application in imaging the generation of intracellular and extracellular ONOO-. Furthermore, exogenous and endogenous ONOO- products in live zebrafish were visualized. It is greatly expected that the designed probe can serve as a useful imaging tool for clarifying the distribution and pathophysiological functions of ONOO- in cells and zebrafish.

miR-150-5p inhibits nasopharyngeal cancer genesis by suppressing PYCR1.

BACKGROUND: Nasopharyngeal cancer (NPC) is a rare cancer type with a low five-year survival rate. Dysregulation of PYCR1 and miR-150-5p has been involved in the development of various cancers. However, the molecular mechanism of the miR-150-5p-PYCR1 axis in NPC remains unclear. METHODS: The expressions of miR-150-5p and PYCR1 in NPC tissues and cells were measured by RT-qPCR. The luciferase assay and RNA pull-down assay were used to confirm the interaction between miR-150-5p and PYCR1. The function of overexpression of miR-150-5p and PYCR1 were detected by cell viability, proliferation, migration and invasion in NPC C666-1 and SUNE-1 cells. RESULTS: The miR-150-5p expression was reduced in NPC tissues and cells and negatively correlated with PYCR1 level. Upregulation of miR-150-5p conspicuously repressed cell growth. However, upregulation of PYCR1 significantly facilitated the development of NPC, which further suppressed NPC tumorigenesis by abolishing the effect of miR-150-5p. CONCLUSIONS: We clarified that miR-150-5p attenuated NPC tumorigenesis through reducing PYCR1 expression. This provides a new perspective of NPC involving both miR-150-5p and PYCR1 for the treatment of NPC.

A ratiometric water-soluble fluorescent probe for the detection of sulfur dioxide derivative in sinusitis mice model.

Sulfur dioxide (SO2) plays an extremely important role in the basic processes of physiology and pathology. As an antioxidant, SO2 can maintain the redox homeostasis in the cell. Excessive inhalation of SO2 would lead to irreparable respiratory damage, resulting in respiratory diseases, neurological disorders, and even cardiovascular disease. Thus, it is urgent to exploit an excellent way to monitor SO2 derivatives in biological system. Herein, we design a water-soluble ratiometric fluorescent probe to fast detect the level of SO2 derivatives in living cells in vivo. The probe displays obvious fluorescence signal at long wavelength, which is helpful for imaging of biological system. After respond to SO2 derivatives, the fluorescence signal at 465 nm increases rapidly due to the Michael addition reaction is triggered, further causing the disruption of large conjugated system. The probe exhibits high selectivity and fast respond to SO2 derivatives, which can be able to sensitive and real-time monitoring of SO2 derivatives level in living cells. Moreover, the probe reveals a low detection limit and a great linear relationship to SO2 derivatives. Based on the negligible cytotoxicity and good biocompatibility of the probe, which is employed to detect exogenous and endogenous SO2 derivatives in living cells. In addition, it is also served as a potential chemical tool to detect SO2 derivatives in mice model of sinusitis.

MicroRNA hsa-miR-150-5p inhibits nasopharyngeal carcinogenesis by suppressing PYCR1 (pyrroline-5-carboxylate reductase 1).

Nasopharyngeal cancer is a rare cancer type, but with a low five-year survival rate. Dysregulation of pyrroline-5-carboxylate reductase 1 (PYCR1) and microRNA hsa-miR-150-5p is involved in the development of various cancers. However, the molecular mechanism of the hsa-miR-150-5p-PYCR1 axis in nasopharyngeal cancer remains unclear. To identify the mechanism of the hsa-miR-150-5p-PYCR1 axis, the expression of hsa-miR-150-5p and PYCR1 in nasopharyngeal cancer tissues and cells was first measured by reverse transcription quantitative polymerase chain reaction. The luciferase and RNA pull-down assays were used to confirm the interaction between hsa-miR-150-5p and PYCR1. The overexpression of hsa-miR-150-5p and PYCR1 was detected by cell viability, proliferation, western blotting, migration, and invasion in nasopharyngeal cancer cells. The expression levels of hsa-miR-150-5p was reduced in the nasopharyngeal cancer tissues and cells and were negatively correlated with the PYCR1 levels. The upregulation of hsa-miR-150-5p significantly repressed cell growth and promoted apoptosis. However, the upregulation of PYCR1 expression significantly promoted nasopharyngeal carcinogenesis, which could abolish the inhibitory effect of hsa-miR-150-5p. In conclusion, we clarified that hsa-miR-150-5p attenuated nasopharyngeal carcinogenesis by reducing the PYCR1 expression levels. This provides a new perspective of nasopharyngeal cancer involving both hsa-miR-150-5p and PYCR1 for the treatment of nasopharyngeal cancer.

A semi-naphthorhodafluor-based red-emitting fluorescent probe for tracking of hydrogen polysulfide in living cells and zebrafish.

Hydrogen polysulfides (H2Sn, n ≥ 2) is recently regarded as a potential signaling molecule which shows a higher efficiency than hydrogen sulfides (H2S) in regulating enzymes and ion channels. However, the development of specific fluorescent probes for H2Sn with long-wavelength emission (>600 nm) are still rare. In this work, a semi-naphthorhodafluor-based red-emitting fluorescent probe SNARF-H2Sn containing a phenyl 2-(benzoylthio) benzoate responsive unit was constructed. SNARF-H2Sn was capable of selectively detecting H2Sn over other reactive sulfur species. Treatment with H2Sn would result in a > 1000-fold fluorescence enhancement within 10 min. SNARF-H2Sn showed a low limit of detection down to 6.7 nM, and further enabled to visualize exogenous/endogenous H2Sn in living A549 cells and zebrafish.

Development of an ultrafast fluorescent probe for specific recognition of hypochlorous acid and its application in live cells.

Hypochlorous acid (HOCl), a highly potent oxidant of reactive oxygen species, plays critical roles in many physiological and pathological processes. In this work, a novel coumarin-based fluorescent probe, Cou-HOCl, was prepared for the detection of HOCl. The probe exhibited good selectivity over other analytes, excellent sensitivity with a detection limit of 16 nM, and fast response within 5 s. And further study demonstrated that the probe could be used not only to image exogenous HOCl in various cells, but also to determine the fluctuating levels of HOCl in macrophage cells during inflammation.

Sensitive and effective imaging of carbon monoxide in living systems with a near-infrared fluorescent probe.

CO, a gas molecule that is harmful to living organisms, has a high affinity with hemoglobin, which will cause severe hypoxia. However, in recent years, researchers have discovered that endogenous CO, similar to NO, is one of the messenger molecules, which has a certain regulatory effect in many physiological and pathological processes in the respiratory system, cardiovascular system, and nervous system. Therefore, it is urgent to explore an effective method to monitor the role of CO under physiological and pathological conditions. Herein, we designed and synthesized a near-infrared small-molecule fluorescent probe for the detection of CO in living cells. In this design, a two-site BODIPY dye was introduced as the fluorophore, and the allyl chloroformate part as the CO reactive group. The probe displays excellent sensitivity, selectivity, and a good linear relationship to CO. Furthermore, it shows good biocompatibility and low cytotoxicity. This probe has been successfully applied to the detection of CO in a variety of cells. The developed fluorescent probe can serve as a potential molecular imaging tool for in vivo imaging and detection of CO.