Hypochlorite (ClO − ), as a type of reactive oxygen species (ROS), plays a crucial role in the process of oxidative stress and is closely related to many diseases. Thus, developing a method for detecting and imaging of ClO − with high sensitivity and selectivity is of great significance. However, the applications of most luminescent probes are limited to the fact that the excitation and emission wavelengths of them are in the visible light region rather than in the near-infrared (NIR) region. Hence, an NIR iridium(III) complex (Mul-NIRIr) with two-photon excitation is designed for the detecting and imaging of ClO − . In the presence of ClO − , the luminescent intensity and lifetime of Mul-NIRIr are remarkably enhanced. Interestingly, Mul-NIRIr also exhibits excellent electrochemiluminescence (ECL) properties, and the ECL signal is significantly enhanced with the addition of ClO − . What is more, Mul-NIRIr is also suitable for the detection and analysis ClO − by flow cytometry. Therefore, Mul-NIRIr is developed to detect multiple signals and is successfully applied to detect exogenous and endogenous ClO − in living cells with one-photon, two-photon, and phosphorescence lifetime image microscopy (PLIM). In addition, Mul-NIRIr was successfully used for imaging of ClO − in tissues and inflammatory mouse models. All of the above results indicate that Mul-NIRIr is highly effective in detecting ClO − in living systems.

The bark, leaves, and flowers of Paulownia trees have been used in traditional Chinese medicine to treat infectious and inflammatory diseases. We investigated the antiviral effects of Paulownia tomentosa flowers, an herbal medicine used in some provinces of P. R. China for the treatment of skin rashes and blisters. Dried flowers of P. tomentosa were extracted with methanol and tested for antiviral activity against enterovirus 71 (EV71) and coxsackievirus A16 (CAV16), the predominant etiologic agents of hand, foot, and mouth disease in P. R. China. The extract inhibited EV71 infection, although no effect was detected against CAV16 infection. Bioactivity-guided fractionation was performed to identify apigenin as an active component of the flowers. The EC 50 value for apigenin to block EV71 infection was 11.0 µM, with a selectivity index of approximately 9.3. Although it is a common dietary flavonoid, only apigenin, and not similar compounds like naringenin and quercetin, were active against EV71 infection. As an RNA virus, the genome of EV71 has an internal ribosome entry site that interacts with heterogeneous nuclear ribonucleoproteins (hnRNPs) and regulates viral translation. Cross-linking followed by immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that EV71 RNA was associated with hnRNPs A1 and A2. Apigenin treatment disrupted this association, indicating that apigenin suppressed EV71 replication through a novel mechanism by targeting the trans-acting factors. This study therefore validates the effects of Paulownia against EV71 infection. It also yielded mechanistic insights on apigenin as an active compound for the antiviral activity of P. tomentosa against EV71 infection.

No abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with short survival time. However, owing to the unknown etiology and the lack of sensitive and noninvasive methods, the diagnosis of IPF in the early stage is still full of challenges. Since the levels of oxidative stress in mitochondria are relevant to pulmonary fibrosis, we herein present a simultaneous near-infrared (NIR)-Ia window and ratiometic fluorescent probe, rTPONOO-1, with two-photon and mitochondria-targeting abilities to explore the potential biological roles of peroxynitrite (ONOO − ) in different states of lung slices from healthy to lung inflammation and pulmonary fibrosis, and there is a good linear relationship between ratiometric fluorescence changes and the rate of pulmonary fibrosis from hematoxylin and eosin (H&E) and Masson staining. In addition, the therapeutic efficacy of aminoguanidine hemisulfate salt (AG) was also investigated. Thus, rTPONOO-1 has great potential in quickly predicting the progression of pulmonary fibrosis in the early stage and improving effective treatment.

Hypochlorous acid (HClO) acts as a dominant microbicidal mediator in the natural immune system, and the excess production of hypochlorites is related to a series of diseases. Thus, it is vitally important and necessary to develop a highly sensitive and selective method for HClO detection in living systems, and most of fluorescent probes are mainly focused on cells imaging. Besides, accurate HClO quantitative information about individual cells in a large cell population is extremely important for understanding inflammation and cellular apoptosis as well. In our work, a turn-on fluorescent probe has been synthesized, which can selectively and sensitively detect HClO with fast response time. The probe is almost nonfluorescent possibly due to both the spirolactam form of fluorescein and unbridged C═N bonds which can undergo a nonradiative decay process in the excited state. Upon the addition of ClO, the probe was oxidized to ring-opened fluorescent form and the fluorescence intensity was greatly enhanced. In live cell experiments, the probe was successfully applied to image exogenous ClO in HeLa cells and endogenous HClO in RAW 264.7 macrophage cells. In particular, the quantitative information on exogenous and endogenous HClO can also be acquired in flow cytometry. Therefore, the probe not only can image exogenous and endogenous HClO but also provides a new and promising platform to quantitatively detect HClO in flow cytometry.