Chlorogenic acid attenuates deoxynivalenol-induced apoptosis and pyroptosis in human keratinocytes via activating Nrf2/HO-1 and inhibiting MAPK/NF-κB/NLRP3 pathways.

Deoxynivalenol (DON) is a common mycotoxic contaminant, frequently found in food and feed, causing a severe threat to human and animal health. Because of the widespread contamination of DON, humans involved in agricultural practices may be directly exposed to DON through the skin route. Chlorogenic acid (CGA) is a phenolic acid, which has anti-inflammatory and antioxidant properties. However, it is still unclear whether CGA can protect against DON-induced skin damage. Here, the effect of CGA on mitigating damage to human keratinocytes (HaCaT) triggered by DON, as well as its underlying mechanisms were investigated. Results demonstrated that DON exposure significantly decreased cell viability, and induced excessive mitochondrial reactive oxygen species (mtROS) generation, mitochondrial damage, oxidative stress, cell apoptosis and pyroptosis. However, CGA pretreatment for 2 h significantly increased cell viability and reversed DON-induced oxidative stress by improving antioxidant enzyme activities such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), reducing mtROS generation and enhancing mitochondrial function through activating Nrf2/HO-1 pathway. Moreover, CGA significantly increased the Bcl-2 protein expression, decreased the protein expressions of Bax and cleaved Caspase-3, and suppressed the phosphorylated of ERK, JNK, NF-κB. Further experiments revealed that CGA could also inhibit the pyroptosis-related protein expressions including NLRP3, cleaved Caspase-1, GSDMD-N, cleaved IL-1ß and IL-18. In conclusion, our results suggest that CGA could attenuate DON-induced oxidative stress, inflammation, and apoptosis by activating the Nrf2/HO-1 pathway and inhibiting MAPK/NF-κB/NLRP3 pathway. CGA might be a novel promising therapeutic agent for alleviating the dermal damage triggered by DON.

CRISPR-based quantum dot nanobead lateral flow assay for facile detection of varicella-zoster virus.

Varicella-zoster virus (VZV) infects more than 90% of the population worldwide and has a high incidence of postherpetic neuralgia in elderly patients, seriously affecting their quality of life. Combined with clustered regularly interspaced short palindromic repeats (CRISPR) system, we develop a quantum dot nanobeads (QDNBs) labeled lateral flow assay for VZV detection. Our assay allows the identification of more than 5 copies of VZV genomic DNA in each reaction. The entire process, from sample preparation to obtaining the results, takes less than an hour. In 86 clinical vesicles samples, the test shows 100% concordance with quantitative real-time PCR for VZV detection. Notably, when vesicles are present in specific areas, such as the genitals, our method outperforms clinical diagnosis. Compared to traditional detection methods, only a minute amount of blister fluid is required for accurate detection. Therefore, we anticipate that our method could be translated to clinical applications for specific and rapid VZV detection. KEY POINTS: • CRISPR/Cas12a and quantum dot nanobead-based lateral flow assay achieved 5 copies per reaction for VZV detection • Specific identification of VZV in atypical skin lesions • Results read by the naked eye within one hour.

Luteolin-Loaded Nanoparticles for the Treatment of Melanoma.

Background and Purpose: Luteolin (LUT), a flavonoid found in various plants, has been reported to have potential therapeutic effects in melanoma. However, poor water solubility and low bioactivity have severely restricted the clinical application of LUT. Based on the high reactive oxygen species (ROS) levels in melanoma cells, we developed nanoparticles encapsulating LUT with the ROS-responsive material poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) to enhance the water solubility of LUT, accelerate the release of LUT in melanoma cells, and further enhance its anti-melanoma effect, providing a viable solution for the application of LUT nano-delivery systems in melanoma therapy. Methods: In this study, LUT-loaded nanoparticles were prepared with PPS-PEG and named as LUT-PPS-NPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were applied to determine the size and morphology of LUT-PPS-NPs. In vitro studies were carried out to determine the uptake and mechanism of LUT-PPS-NPs by SK-MEL-28 melanoma cells. According to the CCK-8 assay, the cytotoxic effects of LUT-PPS-NPs on human skin fibroblasts (HSF) and SK-MEL-28 cells were assessed. Apoptosis assays, cell migration and invasion assays, and proliferation inhibition assays with low and normal density plating were also applied to test the in vitro anti-melanoma effect. Additionally, melanoma models were established utilizing BALB/c nude mice and initially evaluated the growth inhibitory impact following intratumoral injection of LUT-PPS-NPs. Results: The size of LUT-PPS-NPs was 169.77 ± 7.33 nm with high drug loading (15.05 ± 0.07%). In vitro, cellular assays confirmed that LUT-PPS-NPs were efficiently internalized by SK-MEL-28 cells and showed low cytotoxicity against HSF. Moreover, LUT released from LUT-PPS-NPs significantly inhibited tumor cell proliferation, migration and invasion. Animal experiments showed that LUT-PPS-NPs inhibited tumor growth more than 2-fold compared with the LUT group. Conclusion: In conclusion, the LUT-PPS-NPs developed in our study enhanced the anti-melanoma effect of LUT.

Integrative analysis of multi-omics data for liquid biopsy.

The innovation of liquid biopsy holds great potential to revolutionise cancer management through early diagnosis and timely treatment of cancer. Integrative analysis of different tumour-derived omics data (such as genomics, epigenetics, fragmentomics, and proteomics) from body fluids for cancer detection and monitoring could outperform the analysis of single modality data alone. In this review, we focussed on the discussion of early cancer detection and molecular residual disease surveillance based on multi-omics data of blood. We summarised diverse types of tumour-derived components, current popular platforms for profiling cancer-associated signals, machine learning approaches for joint analysis of liquid biopsy data, as well as multi-omics-based early detection of cancers, molecular residual disease monitoring, and treatment response surveillance. We also discussed the challenges and future directions of multi-omics-based liquid biopsy. With the development of both experimental protocols and computational methods dedicated to liquid biopsy, the implementation of multi-omics strategies into the clinical workflow will likely benefit the clinical management of cancers including decision-making guidance and patient outcome improvement.