The suppressor of cytokine signalling 3 (SOCS3) negatively regulates the Janus kinase (JAK)/signal transducer and activator of transcription-3 (STAT-3)/interleukin (IL)-17 pathway. The proinflammatory cytokine IL-17 is over-expressed in Sjögren's syndrome (SS) and is a key factor in its pathogenesis. We hypothesized that IL-17 over-expression in SS results from ineffective regulation by SOCS3. The expression of SOCS3 was analysed in peripheral blood mononuclear cells (PBMC) from SS cases, sicca controls (SC) and healthy controls (HC) and tissue samples from SS, SC and healthy salivary glands (HSG). PBMC and salivary gland tissue from SS and controls were dual-immunostained for SOCS3 and IL-17. IL-6-stimulated PBMC from SS and controls were evaluated for time-dependent STAT-3 activation and SOCS3 induction, and for IL-17 expression. Immunoblotting revealed greater levels of SOCS3 in PBMC from SS than SC (P = 0·017) or HC (P < 0·001). Similarly, the proportion of salivary-gland tissue cells staining for SOCS3 was significantly higher in SS than SC (P = 0·029) or HSG (P = 0·021). The cells in PBMC/salivary gland samples from controls predominantly expressed either SOCS3 or IL-17. However, there was a high frequency of SOCS3/IL-17 co-expression within cells of SS samples. IL-6-stimulation of PBMC from SS cases revealed prolonged activation of STAT-3 with reduced negative regulation by SOCS3, and enhanced expression of IL-17. This study showed that SOCS3 expression is up-regulated in SS. However, the absence in SS of the normal inverse relationship between SOCS3 and pSTAT-3/IL-17 indicates a functional disturbance in this signalling cascade. Consequently, a reduction in function, rather than a reduction in expression of SOCS3 accounts for the unregulated expression of IL-17 in SS, and may play a crucial role in aetiopathogenesis.

Background Micro-ribonucleic acids (miRNA) are key regulators for the expression of related target genes and their aberrant expression has a substantial role across many pathways within autoimmunity. Aim of the work To evaluate the expression of miRNA-146a-5p in systemic lupus erythematosus (SLE) patients and to assess its relation to the disease activity and various disease parameters with specific focus on the ocular manifestations. Patients and methods 42 female SLE patients and 39 matched healthy individuals were enrolled in this study. The serum level of miRNA146a-5p was evaluated by a quantitative real-time polymerase chain reaction (PCR) (Taqman technology). Results The mean age of the patients was 29 ± 9.1 years. The serum level of miRNA146a-5p was significantly higher in SLE cases (3.21 ± 4.47 fold change) compared to the controls (1.54 ± 1.66 fold change) (p = 0.001). A significant negative association was found between the serum level of miRNA146a-5p and C4 level (p = 0.018). Expression levels of miRNA146a-5p were significantly decreased in patients with photosensitivity (p = 0.006). Regarding ocular manifestations, a lower level of miRNA146a-5p was detected in patients suffering from dry eyes, cataract, keratitis and drusen compared to patients without and a higher level was found in those suffering from retinopathy. Serum miRNA146a-5p at a cut off value of 1.36 could discriminate patients from controls (95%CI: 0.61–0.84; p = 0.001) at a sensitivity of 69% and specificity of 64.1%. Conclusion These findings suggest that miR-146a-5p could be a potential diagnostic biomarker in SLE and may implicate a functional role in the pathophysiology of the ocular manifestations in the disease.

A GNPS molecular networking approach mapped a library of 960 southern Australian marine sponges and prioritized Dysidea sp. (CMB-01171) for chemical investigation. Although the published natural products literature on Australian Dysidea sponges extends back over half a century and suffers from the perception of being near exhausted, fractionation of Dysidea sp. (CMB-01171) led to the discovery of a family of 10 new biosynthetically and chemically related sesquiterpenes. Detailed spectroscopic analysis guided structure elucidation identified dysidealactams A-F (1-6), dysidealactones A and B (7 and 8), and two solvolysis artifacts, 9 and 10. The dysidealactams A-D (1-4) incorporate a rare glycinyl-lactam functionality, while dysidealactam E (5) is particularly noteworthy in incorporating an unprecedented glycinyl-imide moiety. In addition to expanding knowledge of Dysidea natural products, this study demonstrates the value of applying GNPS molecular networking to map chemical diversity and prioritize the selection of marine sponge extracts for more detailed chemical analysis.