The NLRP3 inflammasome in viral infection (Review).

The interplay between pathogen and host determines the immune response during viral infection. The Nod­like receptor (NLR) protein 3 inflammasome is a multiprotein complex that induces the activation of inflammatory caspases and the release of IL­1ß, which play an important role in the innate immune responses. In the present review, the mechanisms of the NLR family pyrin domain containing 3 inflammasome activation and its dysregulation in viral infection were addressed.

Nicotine-mediated dopamine regulates short neuropeptide F to inhibit brown planthopper feeding behavior in tobacco-rice rotation cropping.

BACKGROUND: The tobacco-rice rotation cropping (TRRC) is an ecologically friendly system that can both alleviate soil nicotine pollution and decrease the brown planthopper (BPH, Nilaparvata lugens Stål) fitness on rice. However, few studies on this green and effective rotational cropping system have been reported. In particular, the underlying mechanisms of TRRC on the significant reduction of field pest population at the molecular level is still unknown. RESULTS: Field investigation showed that BPH population decreased significantly in TRRC than in rice-rice successive cropping (RRSC) field. In addition, the short neuropeptide F (NlsNPF) and its receptor NlA7 of BPH had half-times lower levels in the TRRC field. Behavioral bioassay indicated a 1.93-fold increase in the number of salivary flanges of the dsNlsNPF group, while BPH fitness parameters, such as honeydew, weight gain, and mortality decreased significantly. Dopamine (DA) content in BPH decreased by ~11.1% under the influence of nicotine, and its presence increased the expression levels of NlsNPF and NlA7. Exogenous DA application eliminated the inhibitory effects of nicotine on BPH feeding and restored the fitness levels of its parameters. Independent application of either a mixture of dsNlsNPF with a nanocarrier or nicotine to the normal rice field revealed that the latter could produce better effects in combination with dsRNA. CONCLUSION: These findings confirmed that DA regulated NlsNPF to inhibit the BPH feeding behavior in TRRC. The results not only provided novel findings on the mechanism of pest-host interactions, but also presented new method for integrated pest management. © 2023 Society of Chemical Industry.

Human umbilical cord mesenchymal stem cell treatment alleviates symptoms in an atopic dermatitis-like mouse model.

BACKGROUND: Atopic dermatitis (AD) is one of the most common immune and inflammatory skin disorders, leading to insufferable itching and skin abnormalities that seriously affect life quality of patients. There are still huge unmet needs for long-term and effective disease control, despite currently available therapies. Evidenced by some preclinical and clinical studies of AD treatment with stem cells, stem cell treatment could significantly and effectively ameliorate AD symptoms. OBJECTIVES: To elucidate underlying mechanisms of how stem cells therapy alleviates AD-like symptoms. METHODS: An AD-like mouse model was constructed and treated with mesenchymal stem cells (MSCs) subcutaneously or subcutaneously combined with intravenously. The differentially expressed genes were sorted out from RNA sequencing results of dorsal skin and blood. RESULTS: Two injection routes of MSCs could alleviate AD-like symptoms and pathologic changes of the skin and immune organs. RNA sequencing of dorsal skin sections and blood provided gene expression signatures for amelioration of skin defects, inflammatory and immune modulation by MSCs, as well as common AD molecular markers for the skin and blood, which may benefit for clinical diagnosis. IL-1ß and its signaling pathway were specifically found to be associated with the development of AD-like dermatitis lesions. MSC treatment effectively inhibited the JAK-STAT pathway and receptors of IL-4, IL-13, IL-17, and IgE. CONCLUSIONS: MSC therapy could regulate abnormal immune and inflammatory status in AD. Mechanistic exploration will contribute to the development of personalized AD treatment based on MSCs.

0.5-5% Supramolecular Salicylic Acid Hydrogel is Safe for Long-Term Topical Application and Improves the Expression of Genes Related to Skin Barrier Homeostasis in Mice Models.

Background: As a keratolytic, salicylic acid (SA) can be topically applied in various formulations and doses in dermatology. Supramolecular SA hydrogel, a new SA formulation with higher bioavailability, is developed and commercially available nowadays. However, there still remain concerns that the long-term and continual application of SA at low concentrations may jeopardize the cutaneous barrier properties. Aim of the Study: To reveal the long-term effects of 0.5-5% supramolecular SA hydrogel on the skin barrier in normal mice models. Materials and Methods: The 0.5%, 1%, 2%, and 5% supramolecular SA hydrogel or hydrogel vehicle without SA was applied to mice's shaved dorsal skin once per day respectively. Tissue samples of the dorsal skin were harvested on day 14 and 28 of the serial application of SA for histopathological observation and transcriptomic analysis. Results: Following topical supramolecular SA hydrogel therapy with various concentrations of SA (0.5%, 1%, 2%, and 5%) for 14 days and 28 days, there were no obvious macroscopic signs of impaired cutaneous health and no inflammatory or degenerative abnormalities were observed in histological results. Additionally, the transcriptomic analysis revealed that on day 14, SA dramatically altered the expression of genes related to the extracellular matrix structural constituent. And on day 28, SA regulated gene expression profiles of keratinization, cornified envelope, and lipid metabolism remarkably. Furthermore, the expression of skin barrier related genes was significantly elevated after the application of SA based on RNA-seq results, and this is likely to be associated with the PPAR signaling pathway according to the enrichment analysis. Conclusion: Our findings demonstrated that the sustained topical administration of the 0.5-5% supramolecular SA hydrogel for up to 28 days did no harm to normal murine skin and upregulated the expression of genes related to the epidermal barrier.

RNA sequencing and metabolic analysis of imiquimod-induced psoriasis-like mice with chronic restrain stress.

AIM: Psoriasis is one of the most common dermatological disorders, characterized by increased epidermal hyperplasia and immune cell infiltration. Psychological stress has been reported to contribute to the severity, aggravation, and relapse of psoriasis. However, the exact mechanism involved in psychological stress's impact on psoriasis is still unclear. We aim to investigate the role of psychological stress in psoriasis from a transcriptomic and metabolomic perspective. MAIN METHOD: We developed a chronic restrain stress (CRS)-imiquimod (IMQ)-induced psoriasis-like mouse model and performed a comprehensive comparative transcriptomic and metabolic analysis with control mice, CRS-treated mice, and IMQ-treated mice to investigate how psychological stress affects psoriasis. KEY FINDING: We found that CRS-IMQ-induced psoriasis-like mice showed significant exacerbation of psoriasis-like skin inflammation compared with mice treated with IMQ only. Mice of the CRS + IMQ group showed increased expression of keratinocyte proliferation and differentiation genes, differential regulation of cytokines, and promotion of linoleic acid metabolism. Correlation analysis of differentially expressed genes in the CRS-IMQ-induced psoriasis-like mice and human psoriasis datasets compared with respective controls revealed 96 overlapping genes of which 30 genes showed consistent induced or repressed expression in all human and mouse datasets. SIGNIFICANCE: Our study provides new insights into the effects of psychological stress on psoriasis pathogenesis and the mechanisms involved, which provides clues for development of therapeutics or biomarkers.

Gene Expression Profile Analysis of Human Epidermal Keratinocytes Expressing Human Papillomavirus Type 8 E7.

Background: Human papillomavirus type 8 (HPV8) has been implicated in the progress of non-melanoma skin cancers and their precursor lesions. The HPV8 E7 oncoprotein plays a key role in the tumorigenesis of HPV-associated cutaneous tumors. However, the exact role of HPV8 E7 in human epidermal carcinogenesis has not been fully elucidated. Methods: To investigate the potential carcinogenic effects of HPV8 E7 on epithelial cells, we used RNA-sequencing technology to analyze the gene expression profile of HPV8 E7-overexpressed normal human epidermal keratinocytes (NHEKs). Results: RNA-sequencing revealed 831 differentially expressed genes (DEGs) between HPV8 E7-expressing NHEKs and control cells, among which, 631 genes were significantly upregulated, and 200 were downregulated. Gene ontology annotation enrichment analysis showed that HPV8 E7 mainly affected the expression of genes associated with protein heterodimerization activity, DNA binding, nucleosomes, and nucleosome assembly. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that overexpression of HPV8 E7 affected the expression of gene clusters associated with viral carcinogenesis and transcriptional misregulation in cancer and necroptosis signaling pathways that reportedly play crucial roles in HPV infection promotion and cancer progression. We also found the DEGs, such as HKDC1 and TNFAIP3, were associated with epigenetic modifications, immune regulation, and metabolic pathways. Conclusion: Our results demonstrate that the pro-carcinogenic effect of HPV8 expression in epithelial cells may be attributed to the regulatory effect of oncogene E7 on gene expression associated with epigenetic modifications and immune and metabolic status-associated gene expression. Although our data are based on an in vitro experiment, it provides the theoretical evidence that the development of squamous cell carcinoma can be caused by HPV.

Integrated Transcriptomics and Metabolomics Analyses of Stress-Induced Murine Hair Follicle Growth Inhibition.

Psychological stress plays an important role in hair loss, but the underlying mechanisms are not well-understood, and the effective therapies available to regrow hair are rare. In this study, we established a chronic restraint stress (CRS)-induced hair growth inhibition mouse model and performed a comprehensive analysis of metabolomics and transcriptomics. Metabolomics data analysis showed that the primary and secondary metabolic pathways, such as carbohydrate metabolism, amino acid metabolism, and lipid metabolism were significantly altered in skin tissue of CRS group. Transcriptomics analysis also showed significant changes of genes expression profiles involved in regulation of metabolic processes including arachidonic acid metabolism, glutathione metabolism, glycolysis gluconeogenesis, nicotinate and nicotinamide metabolism, purine metabolism, retinol metabolism and cholesterol metabolism. Furthermore, RNA-Seq analyses also found that numerous genes associated with metabolism were significantly changed, such as Hk-1, in CRS-induced hair growth inhibition. Overall, our study supplied new insights into the hair growth inhibition induced by CRS from the perspective of integrated metabolomics and transcriptomics analyses.