Cinnamaldehyde inhibits psoriasis­like inflammation by suppressing proliferation and inflammatory response of keratinocytes via inhibition of NF­κB and JNK signaling pathways.

Psoriasis is a systemic immune­mediated inflammatory disease characterized by uncontrolled keratinocyte proliferation and poor differentiation. Cinnamaldehyde (CIN) has been shown to inhibit the proliferation and inflammatory response of primary and immortalized immune cells. However, to the best of our knowledge, the role of CIN in the progression of psoriasis remains unclear. Therefore, the present study aimed to investigate the biological role of CIN in psoriasis. To mimic abnormal proliferation and differentiation in keratinocytes in vitro, normal human epidermal keratinocytes (NHEKs) were stimulated with M5 (IL­1α, IL­17A, IL­22, oncostatin M and TNF­α). The viability and proliferation of NHEKs were analyzed using Cell Counting Kit­8 and 5­Ethynyl­2'­deoxyuridine assays, respectively. Western blotting was used to analyze the expression levels of keratin 1, filaggrin and loricrin in NHEKs. The results of the present study revealed that CIN significantly inhibited the proliferation and cell cycle progression, and promoted the differentiation of M5­stimulated NHEKs. CIN also markedly attenuated the extent of oxidative stress­induced damage in M5­stimulated NHEKs. Moreover, CIN ameliorated M5­induced inflammatory injury in NHEKs, as evidenced by the decreased levels of multiple inflammatory factors. Furthermore, CIN notably downregulated the expression levels of phosphorylated (p)­inhibitor of NF­κB, p­p65 and p­JNK in M5­stimulated NHEKs. In conclusion, the present data suggested that CIN may protect NHEKs against M5­induced hyperproliferation and inflammatory injury via inhibition of NF­κB and JNK signaling pathways. These results provide a novel insight on the role of CIN in psoriasis.

miR-384-5p regulates inflammation in Candida albicans-induced acute lung injury by downregulating PGC1ß and enhancing the activation of Candida albicans-triggered signaling pathways.

Acute lung injury (ALI) is one of the most prevalent respiratory syndromes of excessive inflammatory reaction during lung infection. Candida albicans (C. albicans) infection is among the leading causes of ALI. MicroRNAs (miRNAs) regulate the expression of target mRNAs, including those involved in inflammatory processes, by binding to the 3'UTR. To date, the roles of miRNAs in C. albicans-induced ALI remain unclear. In this study, we investigated the role of miR-384-5p in C. albicans-induced ALI and its underlying molecular mechanism. RT-PCR, Western blot, ELISA, Myeloperoxidase (MPO) assay, microRNA target analysis, transient transfection, and luciferase reporter assay were utilized. In vivo study was conducted on mouse model. The expression of miR-384-5p was upregulated and positively correlated with inflammatory cytokine production in lung tissues and RAW264.7 and J774A.1 macrophages infected with C. albicans. The miR-384-5p inhibitor alleviated the inflammatory reaction induced by C. albicans. Target prediction analysis revealed that PGC1ß was a target of miR-384-5p, which was further validated by the PGC1ß 3'-UTR luciferase assay and the inverse correlation between the expression of miR-384-5p and PGC1ß in C. albicans-infected ALI tissues and macrophages. Moreover, macrophages transfected with miR-384-5p mimic exhibited reduced levels of PGC1ß. The suppression of the expression of PGC1ß by C. albicans infection in the macrophages was abrogated by miR-384-5p inhibitor. Then, we demonstrated that PGC1ß played an inhibitory role in C. albicans-induced production of inflammatory cytokines. Furthermore, suppression of miR-384-5p in macrophages inhibited the activation of the NF-κB, MAPK, and Akt signaling pathways triggered by C. albicans, but not the STAT3 pathway. These results demonstrate that miR-384-5p contributes to C. albicans-induced ALI at least in part by targeting PGC1ß and enhancing the activation of the NF-κB, MAPK, and Akt inflammatory signaling pathways. Thus, targeting miR-384-5p might exert a protective effect on C. albicans-induced ALI.

miR-4698-Trim59 axis plays a suppressive role in hepatocellular carcinoma.

microRNAs (miRNAs) are important players in tumor suppression and oncogenesis. In this study, we aimed to explore the role of miR-4698 with its potential target tripartite motif-containing 59 (Trim59), a protein with oncogenic function, in hepatocellular carcinoma (HCC). The expression of miR-4698 was significantly lower in HCC tissues and HCC cell lines compared to normal tissues adjacent to tumors and in normal hepatic cell lines. Overexpression of miR-4698 in HCC cells by transfection of its mimic significantly inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), whereas its antisense oligonucleotides (ASOs) exerted the opposite effect. Trim59 was identified as a target of miR-4698 in miRDB, and consistent with this prediction, the expression of Trim59 was inversely correlated with that of miR-4698 in HCC, and miR-4698 overexpression led to a significant decrease in the luciferase activity of pRL-Trim59-3'-UTR but not mutant pRL-Trim59-3'-UTR. Moreover, the miR-4698 mimic inhibited the expression of Trim59. Overexpression of Trim59 abrogated the inhibitory effects of miR-4698. In conclusion, these data show that the miR-4698-Trim59 axis plays a tumor-suppressive role in HCC.

Transcriptomic study of high­glucose effects on human skin fibroblast cells.

Skin ulcers are a common complication of diabetes mellitus (DM). Fibroblasts are located within the dermis of skin tissue and can be damaged by diabetes. However, the underlying mechanism of how DM affects fibroblasts remains elusive. To understand the effects of DM on fibroblasts, the current study mimicked DM by high­glucose (HG) supplementation in the culture medium of human foreskin primary fibroblast cells, and the analysis of transcriptomic changes was conducted. RNA sequencing­based transcriptome analysis identified that, upon HG stress, 463 genes were upregulated and 351 genes downregulated (>1.5­fold changes; P<0.05). These altered genes were distributed into 20 different pathways. In addition, gene ontology (GO) analysis indicated that 31 GO terms were enriched. Among the pathways identified, nuclear factor κB (NF­κB) pathway genes were highly expressed, and the addition of Bay11­7082, a typical NF­κB signaling inhibitor, blocked the previously observed alterations in plasminogen activator inhibitor 1 (PAI1), an inflammation marker and frizzled class receptor 8 (FZD8), a Wnt signaling gene, expression that resulted from HG stress. Furthermore, an inhibitor of Wnt signaling diminished the role of Bay11­7082 in the regulation of PAI1 expression under HG conditions, suggesting that Wnt signaling may function downstream of the NF­κB pathway to protect fibroblast cells from HG stress. To the best of our knowledge, the current study is the first analysis of transcriptomic responses under HG stress in human fibroblasts. The data provided here may aid the understanding of the molecular mechanisms by which fibroblast cells are damaged in the skin of patients with DM.

Isolation of both Pseudozyma aphidis and Nocardia otitidiscaviarum from a mycetoma on the leg.

We describe a case of mycetoma which typified the classic presentation of the disease: a male farmer with affection of the lower limbs and a history of trauma. The patient presented with a swollen right lower limb showing multiple discharging sinuses for 25 years. Histopathologically, grains were found by HE stain, and clustered yeast-like cells were observed by PAS stain. The distinctive 'dot-in-circle' sign was found through MRI. Besides Nocardia otitidiscaviarum, Pseudozyma aphidis was isolated from deep tissue culture, and the identification of the etiologic species was ascertained by DNA sequencing. Generally speaking, Nocardia otitidiscaviarum is an infrequent cause of mycetoma, and Pseudozyma species are usually isolated from plant material rather than clinical specimens. This is the first case of mycetoma from which both Nocardia otitidiscaviarum and Pseudozyma aphidis were isolated.