Aflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined. We found a decrease in cell viability and an increase in oxidation and apoptosis in human hepatocyte L02 cells after AFB1 exposure. In addition, the intracellular expression of caveolin-1 was increased in response to AFB1 treatment. Downregulation of caveolin-1 significantly alleviated AFB1-induced apoptosis and decreased cell viability, whereas overexpression of caveolin-1 reversed these effects. Further functional analysis showed that caveolin-1 participates in AFB1-induced oxidative stress through its interaction with Nrf2, leading to the downregulation of cellular antioxidant enzymes and the promotion of oxidative stress-induced apoptosis. In addition, caveolin-1 was found to regulate AFB1-induced autophagy. This finding was supported by the effect that caveolin-1 deficiency promoted autophagy after AFB1 treatment, leading to the inhibition of apoptosis, whereas overexpression of caveolin-1 inhibited autophagy and accelerated apoptosis. Interestingly, further investigation showed that caveolin-1 participates in AFB1-induced autophagy by regulating the EGFR/PI3K-AKT/mTOR signaling pathway. Taken together, our data reveal that caveolin-1 plays a crucial role in AFB1-induced hepatic cell apoptosis via the regulation of oxidation and autophagy, which provides a potential target for the development of novel treatments to combat AFB1 hepatotoxicity.

In this review, we comprehensively summarize the fluorescent probes reported in the literature for all known kinds of chemical warfare agents (CWAs).

NORAD (non-coding RNA activated by DNA damage) is a long non-coding RNA (lncRNA) that is upregulated and promotes cell progression in various human types of cancer; however, its function in non-small cell lung cancer (NSCLC) remains unclear. The present study investigated the regulatory function and underlying mechanisms of NORAD in NSCLC. NORAD and miR-136-5p expression were assessed by reverse transcription-quantitative polymerase chain reaction, and proliferation and glycolysis-associated markers were also assessed. Direct miR-136-5p regulation by NORAD was detected using luciferase reporter assay and RNA immunoprecipitation. NORAD was highly expressed in NSCLC tissues and cell lines. NORAD overexpression increased NSCLC proliferation and glycolysis. Further investigation revealed that NORAD serves as a competing endogenous RNA for miR-136-5p. Gain- and loss-of-function experiments confirmed that miR-136-5p reversed the promoting effects of NORAD in NSCLC. Results of the present study indicate that NORAD serves as a growth-promoting lncRNA in NSCLC by suppressing the function of miR-136-5p. NORAD and miR-136-5p interaction may provide a potential target for NSCLC treatment.

Hydrogen sulphide (H2S), the third endogenous gaseous signalling molecule, has attracted attention in biochemical research. The selective detection of H2S in living systems is essential for studying its functions. Fluorescence detection methods have become useful tools to explore the physiological roles of H2S because of their real-time and non-destructive characteristics. Herein we report a near-infrared fluorescent probe, NIR-HS, capable of tracking H2S in living organisms. With high sensitivity, good selectivity and low cytotoxicity, NIR-HS was able to recognize both the exogenous and endogenous H2S in living cells. More importantly, it realized the visualization of endogenous H2S generated in cells overexpressing cystathionine β-synthase (CBS), one of the enzymes responsible for producing endogenous H2S. The probe was also successfully applied to detect both the exogenous and endogenous H2S in living mice. The superior sensing properties of the probe render it a valuable research tool in the H2S-related medical research.

BackgroundSulfur mustard (SM) is a notorious chemical warfare agent that can cause severe acute lung injury (ALI), in addition to other lesions. Currently, effective medical countermeasures for SM are lacking. Bone marrow-derived mesenchymal stromal cells (BMSCs) possess self-renewal and multipotent differentiation capacity. BMSCs can also migrate to inflammation and injury sites and exert anti-inflammatory and tissue repair functions. Here, we report the curative effect of BMSCs on SM-induced ALI in a mouse model.MethodsMice BMSCs were injected into mice via the tail vein 24 h after SM exposure. The distribution of BMSCs in mice was detected by fluorescence imaging. The therapeutic potential of BMSCs was evaluated by the calculating survival rate. The effects of BMSCs on lung tissue injury and repair assessment were examined by staining with H&E and measuring the lung wet/dry weight ratio, BALF protein level, and respiratory function. The effects of BMSCs on the infiltration and phenotypic alteration of inflammatory cells were analyzed by immunohistochemistry and flow cytometry. The levels of chemokines and inflammatory cytokines were examined using the Luminex Performance Assay and ELISA. RNA interference, western blotting, and ELISA were applied to explore the role of the TLR4 signaling pathway in the anti-inflammatory effects of BMSCs. The extent of tissue repair was analyzed by ELISA, western blotting, and immunohistochemistry.ResultsFluorescence imaging indicated that the lung is the major target organ of BMSCs after injection. The injection of BMSCs significantly improved the survival rate (p < 0.05), respiratory function, and related lung damage indexes (wet/dry weight ratio, total proteins in BALF, etc.) in mice. BMSC administration also reduced the level of pro-inflammatory cytokines, chemokines, and inflammatory cell infiltration, as well as affected the balances of M1/M2 and Th17/Treg. Furthermore, solid evidence regarding the effects of BMSCs on the increased secretion of various growth factors, the differentiation of alveolar epithelial cells, and the enhancement of cell barrier functions was also observed.ConclusionBMSCs displayed protective effects against SM-induced ALI by alleviating inflammation and promoting tissue repair. The present study provides a strong experimental basis in a mouse model and suggests possible application for future cell therapy.Electronic supplementary materialThe online version of this article (10.1186/s13287-019-1189-x) contains supplementary material, which is available to authorized users.