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Objective: Treatment with TNF-α inhibitors improve psoriasis with minimize/minor neutrophils infiltration and CXCL-1/8 expression in psoriatic lesions. However, the fine mechanism of TNF-α initiating psoriatic inflammation by tuning keratinocytes is unclear. Our previous research identified the deficiency of intracellular galectin-3 was sufficient to promote psoriasis inflammation characterized by neutrophil accumulation. This study aims to investigate whether TNF-α participated in psoriasis development through dysregulating galectin-3 expression., Methods: mRNA levels were assessed through quantitative real-time PCR. Flow cytometry was used to detect cell cycle/apoptosis. Western blot was used to evaluate the activation of the NF-κB signaling pathway. HE staining and immunochemistry were used to detect epidermal thickness and MPO expression, respectively. Specific small interfering RNA (siRNA) was used to knock down hsa-miR-27a-3p while plasmids transfection was used to overexpress galectin-3. Further, the multiMiR R package was utilized to predict microRNA-target interaction., Results and Discussion: We found that TNF-α stimulation altered cell proliferation and differentiation and promoted the production of psoriasis-related inflammatory mediators along with the inhibition of galectin-3 expression in keratinocytes. Supplement of galectin-3 could counteract the rise of CXCL-1/8 but not the other phenotypes of keratinocytes induced by TNF-α. Mechanistically, inhibition of the NF-κB signaling pathway could counteract the decrease of galectin-3 and the increase of hsa-miR-27a-3p expression whereas silence of hsa-miR-27a-3p could counteract the decrease of galectin-3 expression induced by TNF-α treatment in keratinocytes. Intradermal injection of murine anti-CXCL-2 antibody greatly alleviated imiquimod-induced psoriasis-like dermatitis., Conclusion: TNF-α initiates psoriatic inflammation by increasing CXCL-1/8 in keratinocytes mediated by the axis of NF-κB-hsa-miR-27a-3p-galectin-3 pathway.

This study focused on an ozone pollution event occurring in winter (January) in Guangzhou. Various influencing factors were analyzed, including various atmospheric trace gases, meteorological conditions during the whole pollution process, as well as the characteristics of the main O 3 precursor volatile organic compounds (VOCs). The main sources of VOCs and the O 3 formation regime were analyzed using an array of tools:the ozone potential formation (OFP), positive matrix factorization (PMF) model, and empirical kinetic modeling approach (EKMA) curve. Feasible strategies for O 3 control were suggested. The results showed that O 3 and NO 2 exceeded the corresponding standards in this winter pollution event, when the concentrations of PM 10 and PM 2.5 were also high, differing from the air pollution characteristics in summer and autumn. Low boundary layer height (<75 m) and high atmospheric stability at night exacerbated the accumulation of ozone precursors and fine particles. Meteorological conditions such as the increased daytime temperature (5℃), stronger solar radiation (10%), and low horizontal wind speed (<1 m·s -1 ) favored photochemical reactions and promoted the formation of ozone and fine particles. VOCs were mainly composed of alkanes, and the proportions of alkanes and alkynes in winter were higher than those in the other seasons. Aromatics (xylenes and toluene) and propylene were the key VOCs species leading to O 3 formation. The main VOCs sources were vehicle exhaust (22.4%), solvent usage (20.5%), and industrial emissions (17.9%); however, the source with highest OFP was identified as solvent usage. O 3 formation in this event was in the VOCs-limited regime, and reducing O 3 precursors in the VOCs/NO x ratio of 3:1 was effective and feasible for O 3 control. This study explored the causes of an O 3 pollution event in winter, which will serve as reference for the synergistic control of O 3 and PM 2.5 in heavy pollution seasons.

Microabscess of neutrophils in epidermis is one of the histological hallmarks of psoriasis. The axis of neutrophil-keratinocyte has been thought to play a critical role in the pathogenesis of psoriasis. However, the features and mechanism of interaction between the two cell types remain largely unknown. Herein, we found that blood neutrophils were increased in psoriasis patients, positively correlated with disease severity and highly expressed CD66b, but not CD11b and CD62L compared to healthy controls. Keratinocytes expressed high levels of psoriasis-related inflammatory mediators by direct and indirect interaction with neutrophils isolated from psoriasis patients and healthy controls. The capacity of neutrophils in provoking keratinocytes inflammatory response was comparable between the two groups and is dependent on IL-17A produced by itself. Neutrophils isolated from psoriasis patients displayed more transcriptome changes related to integrin and increased migration capacity toward keratinocytes with high CD11b expression on cell surface. Of interest, neutrophils were more susceptible to keratinocyte stimulation than to fibroblasts and human umbilical vein endothelial cells (HUVECs) in terms of CD11b expression and the production of ROS and NETs. In conclusion, neutrophils from psoriasis patients gain a strong capacity of IL-17A production and integrins expression that possibly facilitates their abilities to promote production of psoriasis-related inflammatory mediators and migration, a phenomenon likely induced by their interaction with keratinocytes but not with fibroblasts. These findings provide a proof-of-concept that development of new drugs targeting migration of neutrophils could be a more specific and safe solution to treat psoriasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Shi, Lu, Hong, Qiu, Tan, Xiong, Guo and Wang.)

Background: Radiotherapy is one of the main therapeutic approaches for non-small cell lung cancer (NSCLC). However, radioresistant cancer cells can eventually cause tumor relapse and even fatal metastasis. It is thought that radioresistance and metastasis could be potentially linked by epithelial-mesenchymal transition (EMT). In this study, we established radioresistant NSCLC cells to investigate the potential relationship among radioresistance, EMT, and enhanced metastatic potential and the underlying mechanism involving liver kinase B1 (LKB1)-Salt-inducible kinase 1 (SIK1) signaling., Methods: The radioresistant cell lines A549R and H1299R were generated by dose-gradient irradiation of the parental A549 and H1299 cells. The radioresistance/sensitivity was evaluated by Cell Counting Kit-8 assay, apoptosis analysis, and/or clonogenic cell survival assay. The EMT phenotype and the signaling change were assessed by Western blotting. The abilities of invasion and migration were evaluated by transwell assays and wound healing assays., Results: The radioresistant cell lines A549R and H1299R displayed mesenchymal features with enhanced invasion and migration. Mechanistically, A549R and H1299R cells had attenuated LKB1-SIK1 signaling, which leaded to the up-regulation of Zinc-finger E-box-binding homeobox factor 1 (ZEB1)--a transcription factor that drives EMT. Re-expression of LKB1 in A549R cells reversed the EMT phenotype, whereas knockdown of LKB1 in H1299R cells further promoted the EMT phenotype. Moreover, re-expression of LKB1 in A549 cells increased the radiosensitivity, whereas knockdown of LKB1 in H1299 cells decreased the radiosensitivity., Conclusions: Our findings suggest that attenuated LKB1-SIK1 signaling promotes EMT and radioresistance of NSCLC cells, which subsequently contributes to the enhanced metastatic potential. Targeting the LKB1-SIK1-ZEB1 pathway to suppress EMT might provide therapeutic benefits.

Silver nanoparticles (AgNPs) are widely used commercially because of their antibacterial properties. Oxidative stress is known to be involved in the toxicity of AgNPs to bacteria, animals, and algae. The authors used Spirodela polyrhiza to investigate whether AgNPs can induce oxidative stress in higher plants. Results showed that there was a dose-dependent increase in levels of reactive oxygen species, superoxide dismutase and peroxidase activity, and the antioxidant glutathione content in 6-nm AgNP treatments. Catalase activity and malondialdehyde content in 6-nm AgNP treatments was significantly higher than the control at silver concentrations of 5 mg L(-1) . Superoxide dismutase and catalase activity and antioxidant glutathione and malondialdehyde content were not significantly different at 10 mg L(-1) of AgNPs (6 nm and 20 nm). Treatment with 20 µg L(-1) Ag(+) (the amount almost equal to 10 mg L(-1) AgNPs released) did not change the reactive oxygen species level or antioxidant enzymes activity. Micron-sized Ag particles had no effect on S. polyrhiza. Transmission electron microscopy showed that, compared with the control, chloroplasts in S. polyrhiza treated with 6-nm and 20-nm AgNPs accumulated starch grains and had reduced intergranal thylakoids. These results clearly indicate that AgNPs are able to cause oxidative stress and affect the chloroplast structure and function of S. polyrhiza, and this effect was not caused by Ag(+) released from particles., (© 2014 SETAC.)