Background. Psoriasis is an immune-mediated inflammatory chronic skin disease characterized by chronic inflammation in the dermis, parakeratosis, and excessive epidermal growth. MicroRNAs (miRNAs) are key regulators of immune responses. Although differential expression of miRNAs has been reported in certain inflammatory autoimmune diseases, their role in psoriasis has not been fully illuminated. Our aims were to confirm plasma miRNA expression signatures in psoriasis and to examine their potential influence on psoriasis pathogenesis. Methods. A miRNome PCR array was used to analyse the plasma of psoriasis patients and healthy donors. We performed miRNA pathway enrichment and target gene network analyses on psoriasis plasma samples. Results. We found several specific plasma miRNA signatures relevant to psoriasis. The miRNAs targeted pathways associated with psoriasis, such as the VEGF, MAPK, and WNT signaling pathways. Network analysis revealed pivotal deregulated plasma miRNAs and their relevant target genes and pathways regulating psoriasis pathogenesis. Conclusions. This study analysed the expression of plasma miRNAs and their target pathways, elucidating the pathogenesis of psoriasis; these results may be used to design novel therapeutic strategies and to identify diagnostic biomarkers for psoriasis.

BackgroundIncreasing evidence has shown that alterations in the intestinal microbiota play an important role in the pathogenesis of psoriasis. The existing relevant studies focus on 16S rRNA gene sequencing, but in-depth research on gene functions and comprehensive identification of microbiota is lacking.ObjectivesTo comprehensively identify characteristic gut microbial compositions, genetic functions and relative metabolites of patients with psoriasis and to reveal the potential pathogenesis of psoriasis.MethodsDNA was extracted from the faecal microbiota of 30 psoriatic patients and 15 healthy subjects, and metagenomics sequencing and bioinformatic analyses were performed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database, cluster of orthologous groups (COG) annotations, and metabolic analyses were used to indicate relative target genes and pathways to reveal the pathogenesis of psoriasis.ResultsCompared with healthy individuals, the gut microbiota of psoriasis patients displayed an alteration in microbial taxa distribution, but no significant difference in microbial diversity. A distinct gut microbial composition in patients with psoriasis was observed, with an increased abundance of the phyla Firmicutes, Actinobacteria and Verrucomicrobia and genera Faecalibacterium, Bacteroides, Bifidobacterium, Megamonas and Roseburia and a decreased abundance of the phyla Bacteroidetes, Euryarchaeota and Proteobacteria and genera Prevotella, Alistipes, and Eubacterium. A total of 134 COGs were predicted with functional analysis, and 15 KEGG pathways, including lipopolysaccharide (LPS) biosynthesis, WNT signaling, apoptosis, bacterial secretion system, and phosphotransferase system, were significantly enriched in psoriasis patients. Five metabolites, hydrogen sulfide (H2S), isovalerate, isobutyrate, hyaluronan and hemicellulose, were significantly dysregulated in the psoriatic cohort. The dysbiosis of gut microbiota, enriched pathways and dysregulated metabolites are relevant to immune and inflammatory response, apoptosis, the vascular endothelial growth factor (VEGF) signaling pathway, gut-brain axis and brain-skin axis that play important roles in the pathogenesis of psoriasis.ConclusionsA clear dysbiosis was displayed in the gut microbiota profile, genetic functions and relative metabolites of psoriasis patients. This study is beneficial for further understanding the inflammatory pathogenesis of psoriasis and could be used to develop microbiome-based predictions and therapeutic approaches.

The intestinal flora plays an important role in the inflammatory response to the systemic or local infections in the host. A high-calorie diet has been shown to aggravate pneumonia and delay recovery, especially in children. However, the underlying mechanisms remain unclear. Our previous studies demonstrated that a high-calorie diet and LPS atomization synergistically promoted lung inflammation injury in juvenile rats. In this study, specific pathogen-free juvenile rats were placed in a routine environment, and subjected to a high-calorie diet or LPS atomization in isolation as well as combination. Our data revealed that LPS nebulization combined with a high-calorie diet resulted in significant changes in rats, such as slow weight gain, increased lung index, and aggravated lung inflammatory damage. Meanwhile, we found that the aggravation of LPS-induced pneumonia by a high-calorie diet disturbs the balance of Th17/Treg cells. Furthermore, high-throughput sequencing of intestinal contents revealed that a high-calorie diet changed the gut microbiome composition, decreased microbial diversity, and particularly reduced the abundance of the intestinal microbiota associated with the production of short-chain fatty acids (SCFAs) in rats. Consequently, the levels of SCFAs, especially acetate, propionate, and butyrate, were significantly decreased following the intervention of a high-calorie diet. More critically, the effects of a high-calorie diet were shown to be transmissible among pneumonia rats through cohousing microbiota transplantation. Taken together, we provide evidence to support that a high-calorie diet can potentially reset the gut microbiome and metabolites, disrupt Th17/Treg cell balance and immune homeostasis, and aggravate LPS-induced lung inflammatory damage, which may provide a new perspective on the pathogenesis of lung inflammation injury, and suggest a novel microbiota-targeting therapy for inflammatory lung diseases.

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Background: Honeysuckle is a traditional Chinese herbal medicine. It is widely used in the treatment of respiratory infectious diseases in Asia and even worldwide reported in the literature. However, its mechanism remains unclear. Pneumonia is one of the most common clinical manifestations of respiratory infections. This study is aim to find out the molecular mechanism of honeysuckle in the treatment of pneumonia.Methods: LPS-induced pneumonia rats were administered with honeysuckle decoction and compared its efficacy with dexamethasone. The components in honeysuckle decoction were analyzed by liquid-phase mass spectrometry. The target proteins for those components were obtained by database search, target fishing and text mining methods, and then were matched with the genes of pneumonia in the CTD database. Analyzed interactions of target protein by using String database, enrichment analysis by David database, molecular docking was performed by AUTODOCK and PyRx. Its related network diagrams drew by Cytoscape.Results: Our results indicate that honeysuckle can alleviate the inflammation of rat lung tissue to a certain extent, and has similar therapeutic effects as dexamethasone. There are 31 compounds in honeysuckle, and 366 genes associated with these compounds and pneumonia. Among them, 18 of the top 5%, including GAPDH, TNF, FOS, VEGFA, BDNF, etc., were enriched in pathway closely related to pneumonia: Glycine, serine and threonine metabolism, Nitrogen metabolism, and Neuroactive ligand-receptor interaction, etc. The results of molecular docking confirmed that Inosito binds to the PTEN protein of the Phosphatidylinositol signaling system pathway.Conclusions: This study suggests that honeysuckle can play a role in the treatment of pneumonia by affecting multiple targets and pathways, of which Inosito-PTEN-Phosphatidylinositol signaling system may be the most important mechanism. This reflects the multi-target multi-pathway of traditional Chinese medicine, and has a certain specific therapeutic effect on the disease. By interfering with the signaling pathways of the body cells, honeysuckle can be used as a drug candidate for clinical pneumonia treatment.