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Seborrheic dermatitis (SD) is a chronic inflammatory skin condition that occurs in body areas that contain profuse sebaceous glands. Skin microbiota are diverse across ethnic groups and its dysbiosis has been implicated in the pathogenesis of SD. Here, we reported the contribution of cutaneous bacterial microbiota to SD in the Thai population. Healthy individuals and patients with scalp SD were recruited into the study. Normal skin, scalp skin lesion (SL) and non-lesion sites (SNL) samples were collected using a tape stripping method and next-generation sequencing of 16S rRNA for microbiome analysis. Although bacterial diversity in all sample groups was not statistically different, a population of bacteria commonly found on skin of scalp showed signs of dysbiosis. Apart from the reduction of Corynebacterium spp., SD-specific microbiota was dominated by Firmicutes at taxa level and Pseudomonas spp., Staphylococcus spp. and Micrococcus spp. at genus level. The dysbiosis of the skin microbiota in SD was specifically described as an alteration of bacteria populations commonly found on scalp skin, implying that managing and controlling the cutaneous bacterial microbiome can alleviate and prevent SD and pave the way for the development of new SD treatments.

Pinyadapat Vacharanukrauh,1 Jitlada Meephansan,1 Pattarin Tangtanatakul,2 Wipasiri Soonthornchai,3 Jongkonnee Wongpiyabovorn,4 Onsiri Serirat,5 Mayumi Komine6 1Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand; 2Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand; 3Demonstration School, University of Phayao, Phayao, 56000, Thailand; 4Division of Immunology, Department of Microbiology, Faculty of Medicine, Center of Excellence in Immunology and Immune Mediated Diseases, Chulalongkorn University, Bangkok, 10330, Thailand; 5Division of Dermatology, Department of Medicine, Rajavithi Hospital, Ministry of Public Health, Bangkok, 10400, Thailand; 6Department of Dermatology, Jichi Medical University, Tochigi, JapanCorrespondence: Jitlada MeephansanDivision of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Klong Luang, Pathum Thani, 12120, ThailandTel +662564-4444, ext.1535Fax +662564-4440, ext.7594Email kae_mdcu@yahoo.comObjective: To identify the narrowband ultraviolet B (NB-UVB)-induced molecular mechanisms that may account for their anti-inflammatory efficacy, gene expression and transcriptome profiling, which were performed using advanced molecular techniques.Methods: This research was conducted on patients with moderate-to-severe plaque-type psoriasis who received NB-UVB treatment. RNA sequencing (RNA-Seq) was conducted to assay the transcriptomes and identify the differentially expressed transcripts that had been enriched during the major pathway analysis.Results: Clinical improvement of psoriasis by NB-UVB therapy is linked to the suppression of the “immunological signaling pathways” and “cell cycle regulatory, growth and proliferation pathways” which are critical to the pathogenesis of the disease. In addition, these results were further substantiated by demonstrating that NB-UVB therapy has a significant effect on keratinocyte differentiation and affects the regulation of genes and inflammatory mediators that are related to cell proliferation and apoptosis. Moreover, NB-UVB phototherapy is also involved with the downregulation of toll-like receptors signaling in lesional psoriasis.Conclusion: NB-UVB is an effective treatment for psoriasis. Our study supports the conclusion that the clinical effectiveness of NB-UVB therapy is based on the suppression of a broad range of inflammatory signaling pathways, gene expression of inflammatory cytokines and increased expressions of anti-inflammatory signaling pathways in psoriatic skin. This is the first study that applied advanced molecular techniques to investigate phototherapy as a new key to unlock genetic knowledge and create novel information. Ultimately, the goal is to increase medical knowledge and improve the patient care of psoriasis.Keywords: psoriasis, pathogenesis, inflammation, NB-UVB, high-throughput RNA-sequencing, Inflammation, gene, translational study, chronic skin disease, UVB irradiation

Psoriasis is a chronic inflammatory skin condition. It is widely treated with phototherapy using narrowband ultraviolet B (NB-UVB). The therapeutic mechanisms of NB-UVB, however, remain unclear, particularly in the early phases of the disease.To investigate the mechanisms underlying the effects of NB-UVB on psoriasis in a model of perilesional psoriasis.Psoriatic patients that received NB-UVB treatment and were evaluated with the psoriasis area and severity index were included in the study. Skin biopsies obtained before and after treatment were subjected to RNA sequencing (RNA-seq) and Ingenuity Pathway Analyses for genome-wide transcriptome profiling to gain further insights into the signaling pathways underlying the improvement of psoriasis with therapeutic intervention.Our findings revealed that NB-UVB treatment may exert its effects by suppressing nuclear factor kappa B, which leads to upregulation of the sirtuin signaling pathway, as well as by decreasing the function of major upstream regulators associated with proinflammatory and inflammatory cytokines, which blocks the expression of downstream toll-like receptors. Psoriasis improvement after NB-UVB treatment was associated with decreased expression of NFKBIZ, SERPINB4, ATG13, and CTSS and increased expression of SKP1 gene. Our results also highlighted the expression of proposed genes associated with the modulation of autoinflammation.To the best of our knowledge, this is the first study to apply advanced molecular techniques to explore the effects of phototherapy on psoriasis in the early-phase, providing new insights into the disease pathogenesis and novel genetic information for the development of new therapeutic modalities and potential treatment targets.

Psoriasis is a chronic autoimmune skin disease driven by dysregulations at the cellular, genomic and genetic levels. MicroRNAs are key mediators of gene expression regulation. However, how microRNAs control the pathogenesis of psoriasis is still unclear. Here, we reported a significant up-regulation of miR-378a-3p (miR-378a) in skin biopsies from active psoriatic lesions while it was down-regulated after treatment with methotrexate or narrow-band ultraviolet B phototherapy. Using the keratinocyte in vitro model, we showed that miR-378a disturbed the cell cycle progression, causing cell cycle arrest at G1 phase. Transcriptomic analysis of keratinocytes with miR-378a overexpression and depletion revealed several important biological mechanisms related to inflammation and tight junction. Target mRNA transcript assessed by luciferase assay identified bone morphogenetic protein 2 as a novel target gene of miR-378a. These findings offer a mechanistic model where miR-378a contributes to the pathogenesis of psoriasis.

The diagnosis of sepsis-associated encephalopathy (SAE), an alteration of conscious from sepsis, is difficult due to the similarity to altered states of conscious that occur from other causes. Transcriptomic analyses between mouse brains at 24 h after cecal ligation and puncture (CLP) (SAE brain as evaluated by SHIRPA score) and at 120 h post-CLP (survivor) were performed to discover the SAE biomarker. Then, candidate microRNAs were validated in mouse and patient samples.As such, increased miR-370-3p in SAE mouse-brains (compared with recovery phase) was demonstrated by transcriptomic miR-profiling and was highly expressed in brain (but not other organs) of 24 h post-CLP mice. Plasma miR-370-3p also increased in CLP but was non-detectable in bilateral-nephrectomy (BiNx, a representative model of acute uremic encephalopathy) despite blood brain barrier permeability defect (determined by plasma s100β and Evan blue dye assay) in both conditions. In parallel, high plasma miR-370-3p was demonstrated in patients with SAE (but not sepsis alone or uremia) suggesting the specificity toward SAE. The association among TNF-α, miR-370-3p and brain apoptosis was demonstrated by high serum TNF-α and increased brain apoptosis in SAE mice, TNF-α (but not other cytokines) activated miR-370-3p expression in PC-12 neuron cell, and increased cell apoptosis in miR-370-3p transfected PC-12 after incubation with TNF-α.In conclusion, miR-370-3p increased in brain and plasma of SAE mice but not uremic encephalopathy. Perhaps, TNF-α enhances cell susceptibility toward brain apoptosis in SAE, in part, through miR-370-3p induction in neuron. Our pilot results in patients with SAE supported the possibility that plasma miR-370-3p is an interesting SAE biomarker candidate. Further studies are warranted.

Background Psoriasis is a chronic inflammatory skin disease arising from a complex interaction between genetics, epigenetics, the host's immune system and the environment. Recent accumulated data revealed the dysregulation of various microRNAs (miRNAs) in several diseases including psoriasis. Objective We explored the functional role and regulation of hsa-miR-155-5p (miR-155) in an immortalized keratinocyte cell line (HaCaT), in relation to the pathogenesis and treatment of psoriasis. Methods miR-155 expression in normal skin and psoriatic skin lesion before and after treatment with methotrexate (MTX) and narrow-band ultraviolet B phototherapy (NB-UVB) were analyzed using quantitative reverse transcription PCR (qRT-PCR). Apoptotic activity, cell cycle and viable cells of miR-155 transfected HaCaT were measured using flow cytometry and MTS assay. Since, caspase-3 (CASP3) gene was predicted as a target gene of miR-155, the expression of CASP3 was detected in transfected HaCaT using western blot. Results We discovered that both MTX and NB-UVB significantly down-regulated miR-155 expression in psoriatic skin lesions. We also found that overexpression of miR-155 in HaCaT led to suppression of cell apoptosis and induced cell arrest at G0/G1 phase. Moreover, CASP3 expression was down-regulated in miR-155 transfected HaCaT. Conclusion This study demonstrates down-regulation of miR155 after treatment with MTX and NB-UVB in psoriatic skin lesion. miR155 plays significant role in apoptosis on HaCaT via CASP3. This finding provides a better understanding of the pathogenesis of psoriasis and might aid on developing the new monitoring tool or therapy for psoriasis in the future.

Acute Hepatopancreatic Necrosis Disease (AHPND) is an emerging disease in aquacultured shrimp caused by a pathogenic strain of Vibrio parahaemolyticus. As with several pathogenic bacteria, colonization of the stomach appeared to be the initial step of the infection for AHPND-causing Vibrio. To understand the immune responses in the stomach of black tiger shrimp (Penaeus monodon), differentially expressed transcripts (DETs) in the stomach during V. parahaemolyticus strain 3HP (VP3HP) infection was examined using Ion Torrent sequencing. From the total 42,998 contigs obtained, 1585 contigs representing 1513 unigenes were significantly differentially expressed with 1122 and 391 unigenes up- and down-regulated, respectively. Among the DETs, there were 141 immune-related unigenes in 10 functional categories: antimicrobial peptide, signal transduction pathway, proPO system, oxidative stress, proteinases/proteinase inhibitors, apoptotic tumor-related protein, pathogen recognition immune regulator, blood clotting system, adhesive protein and heat shock protein. Expression profiles of 20 of 22 genes inferred from RNA sequencing were confirmed with the results from qRT-PCR. Additionally, a novel isoform of anti-lipopolysaccharide factor, PmALF7 whose transcript was induced in the stomach after challenge with VP3HP was discovered. This study provided a fundamental information on the molecular response in the shrimp stomach during the AHPND infection that would be beneficial for future research.

In all previous studies, to study shrimp immune response, bacteria were directly injected into the shrimp body and as a consequence the initial step of a natural interaction was omitted. In this study we have instead used an immersion technique, which is a more natural way of establishing an infection, to study immune responses in black tiger shrimp (Penaeus monodon). Normally, Vibrio harveyi (Vh) is highly pathogenic to post-larval shrimp, but not to juveniles which usually resist an infection. In post-larvae, Vh causes a massive destruction of the digestive system, especially in the hepatopancreas and in the anterior gut. We have therefore investigated changes in transcription levels of fifteen immune-related genes and morphological changes in juvenile shrimp following an immersion of shrimp in Vh suspension. We found that a pathogenic bacterium, Vh, has the capacity to induce a local expression of some immune-related genes in shrimp after such a bacterial immersion. Our results show that in the juvenile gut small changes in expression of the antimicrobial peptide (AMP) genes such as antilipopolysaccharide factor isoform 3, crustin and penaeidin were observed. However some other genes were more strongly induced in their expression compared to the AMP genes. C-type lectin, Tachylectin 5a1 and mucin-like peritrophic membrane were increased in their expression and the C-type lectin was affected most in its expression. Several other examined genes did not change their expression levels. By performing histology studies it was found that Vh infection induced a strong perturbation of the midgut epithelium in some regions. As a consequence, the epithelial cells and basement membrane of the infected site were completely damaged and necrotic and massive hemocyte infiltration occurred underneath the affected tissue to combat the infection.