The LINC01176-miR-218-5p-IL-36G Network is Responsible for the Pathogenesis of Psoriasis by Promoting Inflammation.

Purpose: Psoriasis is an incurable chronic inflammatory skin disease. The exact function and regulatory mechanism of non-coding RNA upregulation in psoriasis remains to be elucidated. The aim of this study was to analyse the role of the lncRNA-miRNA-mRNA network of psoriasis and LINC01176 in the pathogenesis of psoriasis. Patients and Methods: We performed miRNA, lncRNA, and mRNA sequencing analysis in pretreatment and treatment psoriatic tissues and normal tissues, constructed an lncRNA-miRNA-mRNA coexpression network and screened mRNA-associated pathways using bioinformatics analysis. We further validated the regulatory role of LINC01176-miR-218-5p on the proliferation and inflammation of the psoriatic model by dual-luciferase reporter assay, cell transfection, CCK-8 method, TUNEL staining and animal model construction method. An lncRNA-miRNA-mRNA coexpression network was successfully constructed by RNA-seq data analysis. Results: We obtained the relationship between LINC01176, miR-218-5p and IL36-G. Analysis of the apoptotic and proliferative capacity of the transfected cells showed that miR-218-5p up-regulation significantly inhibited cell proliferation and promoted apoptosis. A mouse model of psoriasis was successfully established. Phenotypic observations revealed that keratin-forming cells in mice coated with LINC01176-shRNA emulsifier were significantly lower than those in the model group and close to those in the normal group. HE and immunohistochemical experiments were performed, and the results showed the role and mechanism of action of LINC01176-shRNA. Suppression of LINC01176 significantly inhibited the expression of IL-36G in psoriatic tissues. LINC01176 showed a targeting and positive correlation with IL36-G expression. Conclusion: Our study shows that LINC01176 promotes the proliferation and invasion of keratinocytes and inhibits apoptosis by targeting miR-218-5p, which acts as a repressor of the psoriasis-associated IL-36G. The shRNA-LINC01176 emulsion showed potential treatment capability in alleviating symptoms of psoriasis.

Can Microneedle Fractional Radiofrequency System Treatment Impair the Skin Barrier Function in Chinese Patients? A Prospective Clinical Trial.

INTRODUCTION: Facial cosmetic conditions can manifest as post-inflammatory erythema, scars, pigmentation, enlarged pores, skin laxity, and photoaging. The microneedle fractional radiofrequency system (MFRS) is a new device that combines radiofrequency and microneedles and has been widely used for skin rejuvenation. Since MFRS is an invasive technique, this study aimed to evaluate whether the skin barrier functions might be impaired by this treatment, revealed by skin sensitivity and exacerbation of melasma. METHODS: Twenty patients with Fitzpatrick grades III-IV facial conditions (skin laxity with melasma, n = 9; post-inflammatory erythema and scars, n = 5; and enlarged pores, n = 6) and treated with MFRS were enrolled. Transepidermal water loss (TEWL, using Ultrascan UC22), skin sensitivity (ten-item Sensitive Scale, SS-10), melanin index (MI), melasma area and severity index (MASI), red areas (VISIA), and thickness and density of the epidermis and dermis on ultrasonography were compared between baseline and 6 months after all treatment sessions. RESULTS: Twenty patients completed a 6-month follow-up after two MFRS treatments. During days 1-3 post-treatment, the TEWL values gradually increased to the peak and decreased to baseline levels (BD) on day 7. There was no significant difference in TEWL compared with baseline in month (M) 1, M3, and M6. There were no significant changes in the thickness and density of the epidermis. Although the thickness and density of the dermis increased, there was no significant difference compared to baseline. There was no significant difference in the MI, MASI, and SS-10 score before and after MFRS treatment. After treatment with MFRS, the red area and scarring reduced significantly (p < .01), and no significant difference was observed in other patients. CONCLUSIONS: MFRS is a safe and effective treatment for facial cosmetic conditions. The skin barrier function is not impaired by MFRS treatment, since it does not cause skin sensitivity or melasma exacerbation.

Associations between ERAP1 Gene Polymorphisms and Psoriasis Susceptibility: A Meta-Analysis of Case-Control Studies.

This study is to investigate the relationship of endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms with psoriasis. Five databases of PubMed, China National Knowledge Infrastructure (CNKI), Embase, Web of Science, and Cochrane Library were searched for potential studies until 25 December 2019. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies. Meta-analysis was performed with PRISMA. A total of 9 case-control studies including 4858 psoriasis cases and 10,542 healthy controls were included. Three loci of ERAP1 gene polymorphisms (rs26653, rs30187, and rs27524) were evaluated in this meta-analysis. There was no significant association between rs26653 polymorphism and risk of psoriasis (C vs. G, OR = 1.01, 95% CI: 0.80-1.28, P = 0.93). However, there was a significant association between rs30187 polymorphisms and psoriasis susceptibility (T vs. C, OR = 1.23, 95% CI: 1.15-1.32, P < 0.00001) and a significant association between rs27524 polymorphisms and psoriasis susceptibility (A vs. G, OR = 1.17, 95% CI: 1.09-1.25, P < 0.00001). For there were insufficient data of rs27044, rs151823, rs2248374, and rs2910686, we only conducted a systematic review for them. The rs30187 (C/T) and rs27524 (G/A) polymorphisms of ERAP1 are associated with increased risk of psoriasis. However, no significant association is observed between rs26653 (G/C) polymorphism and risk of psoriasis.

Primary localized cutaneous nodular amyloidosis presenting as lymphatic malformation: A case report.

Primary skin amyloidosis is a chronic skin disease in which amyloid deposits in the normal skin tissues without involving other organs. At present, the causes and mechanisms of morbidity have not been fully elucidated. There are few clinical reports of nodular skin amyloidosis, and the domestic reports are mostly limited cases. This study reported a rare case of a 46-year-old woman with primary localized cutaneous nodular amyloidosis (PLCNA). The patient presented with features of lymphatic malformation, a plexiform nodule of small blisters. Histological examination revealed amyloid deposits involving the superficial and deep dermis with a small number of plasma cells. Further examinations did not reveal evidence of systemic involvement, indicating a PLCNA. The presentation as lymphatic malformation lesions illustrates the importance of clinical pathology. Nodular amyloidosis typically manifests as single or multiple yellow-brown nodules or plaques of a few millimeters to several centimeters. The center of the nodule sometimes shows atrophy and relaxation or forms a bullous. It is recommended to perform a pathological examination to confirm the diagnosis to distinguish it from lymphatic malformation.

Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway.

Acacetin (5,7-dihydroxy-4'-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3 (NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin (acacetin group) or an equal volume of saline (0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1 (Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1ß and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1ß, and interleukin-1ß were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway.

MicroRNA-126 regulates the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) pathway in SLK cells in vitro and the expression of its pathway members in Kaposi's sarcoma tissue.

In vitro, microRNA-126 (miR-126) inhibits SLK cell proliferation, inhibits the cell cycle, induces cell apoptosis, and reduces cell invasiveness. Double luciferase assays have shown that phosphatidylinositol-3 kinase (PI3K) is the miR-126 target in SLK cells. We aimed to investigate the influence of miR-126 on the phosphate and tension homology deleted on chromosome ten (PTEN)/PI3K/protein kinase B (AKT) pathway members in SLK cells and to determine the expression of these pathway members in Kaposi's sarcoma (KS). The mimic and inhibitor of miR-126 were transfected into SLK cells and PTEN and AKT1 expression was assayed in SLK cells by real-time quantitative PCR and western blotting. PTEN, AKT1, phosphorylated (P)-PTEN, and phosphorylated (P)-AKT expression in KS and paraneoplastic skin were assayed by immunohistochemistry. AKT1 expression was downregulated in SLK cells that overexpressed miR-126, while there was no significant difference in PTEN expression between SLK cells overexpressing miR-126 and those in which its expression was knocked down. PTEN and AKT1 were expressed in KS and paraneoplastic skin but P-AKT was not. Interestingly, P-PTEN was not expressed in paraneoplastic skin but it was expressed in 90% of KS biopsies (P < .05). P-PTEN expression was also significantly higher in visceral than in cutaneous KS (P = .01) and was higher in indoor than in outdoor workers (P = .018). In vitro, miR-126 negatively regulated AKT1 expression but no regulation of PTEN expression was evident. Results indicated that in KS, PTEN is activated and may therefore be a potential therapeutic target for KS. In addition, these results also indicate that sunlight may not be the cause of KS.

Differential expression of microRNAs in the normal skin of the Han and Uyghur populations in Xinjiang Province.

In this study, we investigated the expression of microRNAs (miRNAs) in the skin samples from the Han and Uyghur populations in Xinjiang, China. The miRNA levels of the normal skin samples from 10 individuals of Uyghur or Han were tested by microarray and the expression differentiations were compared. Among the 3100 probes for microarray, a total of 247 miRNAs were differentially expressed in the Han versus Uyghur population, including 76 upregulated miRNAs and 171 downregulated miRNAs. The most significantly upregulated miRNAs were miR-141-3p, miR-1915-5p, kshv-miR-K12-2-5p, and miR-222-3p. And the most significantly downregulated miRNAs included miR-1207-3p and miR-625-3p. We have confirmed the upregulation of miR-141-3p and miR-1915-5p by qRT-PCR. There were no statistical correlations in the expression of miR-141-3p or miR-1915-5p with the age or gender within each group. Interestingly, the differentially expressed miRNAs were enriched in some cancer-related pathways, such as p53, mitogen-activated protein kinase, and WNT signal pathways. Collectively, these dysregulated expressions of the miRNAs may provide a better understanding of the differences in the incidence and mortality of skin-related carcinoma between the Uyghur and Han populations in Xinjiang.

MicroRNA-126-3p suppresses cell proliferation by targeting PIK3R2 in Kaposi's sarcoma cells.

Kaposi's sarcoma is a highly vascular tumor of lymphatic endothelial origin. Many deregulated miRNAs, including miR-126-3p, have been identified in Kaposi's sarcoma tissues. miR-126-3p is the most highly endothelial-specific miRNA that regulates vascular integrity and angiogenesis. In this study, we aimed to determine the effect of miR-126-3p on Kaposi's sarcoma cells through transfection of a miRNA mimic and inhibitor. Moreover, we searched the target gene (PIK3R2) of miR-126-3p using bioinformatics software and further verified PIK3R2 using luciferase reporter assays, Real-time quantitative PCR (qRT-PCR) and western blot. The results demonstrated that miR-126-3p inhibited cell proliferation, arrested cell cycle progression, induced cell apoptosis, and inhibited cell invasion of SLK cells. The bioinformatics analysis and luciferase reporter assay revealed that PIK3R2 mRNA is a direct target of miR-126-3p. Moreover, the level of expression of the PIK3R2 gene was downregulated in SLK cells transfected with miR-126-3p siRNAs. Therefore, our data demonstrated that miR-126-3p is a tumor suppressor miRNA that acts by targeting PIK3R2 in Kaposi's sarcoma cells. These findings contribute to our understanding of the molecular mechanisms underlying Kaposi's sarcoma.

The expression profiles of microRNAs in Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a multicentric angioproliferative tumor of mesenchymal origin. The molecular and biologic aspects of KS are not fully understood. MicroRNAs are non-protein-coding small RNAs in the size range 19-25 nucleotides (nt) that play important roles in biological processes, including cellular differentiation, proliferation, and death. We performed a miRNA microarray analysis by detecting six paired KS and matched adjacent healthy tissues using the 7th generation of miRCURY(TM) LNA Array (v.18.0) (Exiqon) containing 3100 capture probes. We selected 10 significant differentially expressed miRNAs, which were confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in 18 paired KS and matched adjacent healthy tissue specimens. We also investigated the associations between clinical features and miRNA expression. Among the 3100 human miRNA probes in the microarrays, we identified 170 differentially expressed miRNAs (69 upregulated and 101 downregulated miRNAs) in KS versus adjacent healthy tissues. Among the most significantly upregulated miRNAs were miR-126-3p, miR-199a-3p, miR-16-5p, and the 13 KSHV-related miRNAs. The most significantly downregulated miRNAs included miR-125b-1-3p and miR-1183. Eight upregulated miRNAs, miR-181b-5p, miR-199a-3p, miR-15a-5p, miR-126-3p, miR-1297, kshv-miR-k12-12-3p, kshv-miR-k12-1-5p, and miR-16-5p, and two downregulated miRNAs, miR-125b-1-3p and miR-1183, were confirmed by qRT-PCR in 18 paired KS samples. The qRT-PCR results for 10 miRNAs were consistent with our microarray results. The miR-125b-1-3p and miR-16-5p had statistically significant associations with HHV-8 and HIV infections in KS. The results of miRNA profiling showed that KS appears to have unique expression patterns when compared with paired adjacent healthy tissues, suggesting that deregulation of miRNAs plays an important role in the progression of KS. These differentially expressed miRNAs may provide novel diagnostic and prognostic tools.