Identification of potential key molecules and signaling pathways for psoriasis based on weighted gene co-expression network analysis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, the pathogenesis of which is more complicated and often requires long-term treatment. In particular, moderate to severe psoriasis usually requires systemic treatment. Psoriasis is also associated with many diseases, such as cardiometabolic diseases, malignant tumors, infections, and mood disorders. Psoriasis can appear at any age, and lead to a substantial burden for individuals and society. At present, psoriasis is still a treatable, but incurable, disease. Previous studies have found that microRNAs (miRNAs) play an important regulatory role in the progression of various diseases. Currently, miRNAs studies in psoriasis and dermatology are relatively new. Therefore, the identification of key miRNAs in psoriasis is helpful to elucidate the molecular mechanism of psoriasis. AIM: To identify key molecular markers and signaling pathways to provide potential basis for the treatment and management of psoriasis. METHODS: The miRNA and mRNA data were obtained from the Gene Expression Omnibus database. Then, differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were screened out by limma R package. Subsequently, DEmRNAs were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomics functional enrichment. The "WGCNA" R package was used to analyze the co-expression network of all miRNAs. In addition, we constructed miRNA-mRNA regulatory networks based on identified hub miRNAs. Finally, in vitro validation was performed. All experimental procedures were approved by the ethics committee of Chinese PLA General Hospital (S2021-012-01). RESULTS: A total of 639 DEmRNAs and 84 DEmiRNAs were identified. DEmRNAs screening criteria were adjusted P (adj. P) value < 0.01 and |logFoldChange| (|logFC|) > 1. DEmiRNAs screening criteria were adj. P value < 0.01 and |logFC| > 1.5. KEGG functional analysis demonstrated that DEmRNAs were significantly enriched in immune-related biological functions, for example, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, and chemokine signaling pathway. In weighted gene co-expression network analysis, turquoise module was the hub module. Moreover, 10 hub miRNAs were identified. Among these 10 hub miRNAs, only 8 hub miRNAs predicted the corresponding target mRNAs. 97 negatively regulated miRNA-mRNA pairs were involved in the miRNA-mRNA regulatory network, for example, hsa-miR-21-5p-claudin 8 (CLDN8), hsa-miR-30a-3p-interleukin-1B (IL-1B), and hsa-miR-181a-5p/hsa-miR-30c-2-3p-C-X-C motif chemokine ligand 9 (CXCL9). Real-time polymerase chain reaction results showed that IL-1B and CXCL9 were up-regulated and CLDN8 was down-regulated in psoriasis with statistically significant differences. CONCLUSION: The identification of potential key molecular markers and signaling pathways provides potential research directions for further understanding the molecular mechanisms of psoriasis. This may also provide new research ideas for the prevention and treatment of psoriasis in the future.

A Retrospective Study of Biliary Drainage Strategies for Patients with Malignant Hilar Biliary Strictures.

PURPOSE: The main aim of this study was to compare the efficacy and safety of different biliary drainage strategies, including percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary stenting (EBS) and unilateral versus bilateral stenting, in patients with unresectable malignant hilar biliary strictures (MHBSs). PATIENTS AND METHODS: This was a retrospective review of patients with inoperable MHBSs who underwent biliary drainage by either EBS or PTBD. Efficacy and safety were compared between the two pathways and between unilateral and bilateral stenting in the EBS group. The survival duration was analyzed with K-M curves and Log rank tests. RESULTS: From January 2015 to December 2019, a total of 206 (126: EBS and 80: PTBD) patients with MHBSs were enrolled in our study and underwent 270 procedures (173: EBS and 97: PTBD). Bilateral stenting was superior to unilateral stenting in terms of clinical success (69.6% vs 50.6%, p=0.039), especially for patients with Bismuth type IV (70.0% vs 30.3%, p=0.002). A higher decrease in bilirubin was seen with PTBD in patients with Bismuth types III-IV (66.9 vs 36.7, p=0.006). A survival advantage was seen in successful drainage (227 days vs 82 days, p<0.001), lower tumor-node-metastasis (TNM) scores (I-II) (195 days vs 139 days, p=0.012), and cholangiocarcinoma (184 days vs 84 days, p=0.001). CONCLUSION: For patients with advanced MHBSs, bilateral stenting may achieve a better drainage effect than unilateral stenting, and PTBD may have a better performance in relieving cholestasis than EBS. Successful drainage and cholangiocarcinoma may provide greater long-term survival benefits.

Erratum: Effects of HPV16E6 transfection on the biological behavior of Eca109 and Eca9706 cells.

[This corrects the article DOI: 10.3892/ol.2017.7469.].

Effects of HPV16E6 transfection on the biological behavior of Eca109 and Eca9706 cells.

The aim of the present study was to investigate the effect of HPV16E6 gene integration on the biological behavior of Eca109 and Eca9706 cells. This was evaluated through positive liposome transfection of HPV16E6 into Eca109 cells and Eca9706 cells. The transfection efficiency was evaluated by calculating the ratio of fluorescent cells to total cells. After stable screening, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the target gene and HPV16E6mRNA inside the cells. The distribution of HPV16E6 in esophageal carcinoma cells was observed by immunofluorescence and western blot analysis. A CCK-8 assay was performed to detect cell proliferation. The migration rate was measured by a wound healing assay, and a Transwell Matrigel invasion assay was used to detect invasive ability. The results of RT-PCR, immunofluorescence and western blot analyses indicated that HPV16E6 gene was expressed in the target group. The proliferation rates and clone group numbers were significantly higher in HPV16E6-transfected cell groups compared with nonsense-transfected (negative control) cell groups. The wound healing and Transwell invasion assays indicated that the migration rate and invasive ability were also significantly higher in the HPV16E6-transfected cell groups compared with negative control groups. In conclusion, Eca109 and Eca9706 cell lines with integration of HPV16E6 were successfully established in the present study. It was demonstrated that HPV16E6 expression enhanced the proliferation and migration of esophageal cancer cells. HPV16E6 may serve a key function in the occurrence and development of esophageal cancer.