Increased expression profile of NCSTN, Notch and PI3K/AKT3 in hidradenitis suppurativa.

BACKGROUND: In a small number of kindreds with familial hidradenitis suppurativa (HS) different mutations of NCSTN (nicastrin) have been identified. Blocking of NCSTN leads to impairment of the Notch and PI3K/AKT signalling pathway, which is assumed to play a pathogenic role in HS. However, very limited data are available concerning expression levels of these pathway components in HS skin. OBJECTIVES: To analyse the mRNA and protein expression of NCSTN, Notch1-3, PIK3R3 and AKT3 in HS. METHODS: Skin samples from healthy controls, lesional and perilesional skin of HS patients with and without a positive family history were analysed by quantitative real-time RT-PCR and immunohistochemistry. Univariate statistical analyses were conducted regarding association between expression levels and patient's characteristics. RESULTS: Expression levels of all investigated genes showed significantly higher levels in lesional HS skin compared with healthy controls. Univariate analysis showed no association between a positive family history and mRNA expression levels. Perilesional HS skin of patients with mild disease severity (Hurley I) showed significant higher mRNA expression levels of the investigated pathway components compared to moderate (Hurley II) and severe disease (Hurley III). CONCLUSION: We found no evidence for diminished expression levels of the Notch signalling. In contrast, the NCSTN, Notch and PI3K/AKT signalling components are overexpressed in HS. Future research is needed to investigate a possible pathogenetic role or to reveal a coactivation of these overexpressed components during inflammatory response in HS.

Frequency of circulating subpopulations of T-regulatory cells in patients with hidradenitis suppurativa.

BACKGROUND: Decreased number of T-regulatory cells (Tregs) and/or their loss of function potentially lead to uncontrolled immune-mediated inflammatory responses. There are only few data available on Tregs in hidradenitis suppurativa (HS) - a disease in which it has been suggested that host immune factors and an overactive immune system of the follicular epithelium play a pathogenetic role. OBJECTIVES: To analyse frequencies of Tregs subpopulations in blood of HS patients in comparison with a healthy control group. MATERIALS & METHODS: Blood samples obtained from HS patients and healthy controls were evaluated by flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The frequency of natural Tregs among CD4+ T lymphocytes were significantly reduced in the HS group compared to the healthy controls. The proportion of activated Tregs, non-suppressive Tregs and proliferating Tregs showed no significant difference when compared to controls. Regarding Tregs frequencies, there was no significant difference between the three Hurley stages. Serum concentrations of IL-10, TGF-ß1 and IL-17A did not show significant differences between the HS and control group. CONCLUSION: The reduction of natural Tregs observed in blood of HS patients could be the result of Tregs homing to sites of inflammatory hot spots in HS skin. Further studies are justified evaluating the role of circulating Tregs during the evolution of HS lesions and as a biomarker for treatment response.

Low Drosha protein expression in cutaneous T-cell lymphoma is associated with worse disease outcome.

BACKGROUND: Dysregulation of microRNAs (miRNAs) key regulators may contribute to the pathogenesis of malignancies. miRNA machinery genes such Dicer and Drosha have been reported to be biomarkers in different cancer types. OBJECTIVES: We aimed to evaluate Drosha and Dicer protein expression in cutaneous T-cell lymphoma (CTCL). METHODS: We performed Drosha and Dicer immunohistochemistry in 45 patients with mycosis fungoides and subtypes. Drosha and Dicer expression scores were correlated with clinical parameters including disease-specific death (DSD), stage of disease and different laboratory data. Uni- and multivariate statistics were performed. RESULTS: On univariate analysis, elevated serum LDH and low Drosha expression were significantly associated with advanced stage (P = 0.032 and 0.0062, respectively) and lymphoma-specific death (LSD; P = 0.017 and P = 0.005, respectively). Moreover, elevated circulating CD4+/CD26- lymphocytes were significantly associated with advanced stage (P = 0.032) and DSD (P = 0.0098). On multivariate analysis, low Drosha expression remained in the logistic regression model as significant independent predictor for advanced disease stages [P = 0.013; odds ratio: 5 (confidence interval) CI 1.3-19.3]. Moreover, low Drosha expression (P = 0.026) and elevated LDH (P = 0.025) remained as significant independent predictors for DSD with odds ratios of 13.5 (CI 1.3-134.4 and 8.7 CI 1.3-57.2, respectively). CONCLUSIONS: Low Drosha expression is an independent predictor for advanced stage as well as LSD in CTCL patients indicating a tumour suppressor gene function of Drosha in this disorder.

Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop.

BACKGROUND: Possible regulatory involvement of the interleukin (IL)-36 family in inflammatory diseases has been suggested. OBJECTIVES: To analyse the expression of IL-36α, IL-36ß, IL-36γ and the antagonistic cytokines IL-36 receptor agonist (IL-36Ra), IL-37 and IL-38 in the skin of patients with hidradenitis suppurativa (HS). METHODS: Skin samples from lesional and corresponding perilesional HS skin, and from healthy controls were included in this study and analysed by quantitative real-time reverse-transcriptase polymerase chain reaction (PCR). To evaluate the PCR results of IL-36α, IL-36ß and IL-36γ, a subset of skin samples was studied by immunohistochemistry. RESULTS: Expression levels of IL-36α, IL-36ß, IL-36γ and IL-36Ra were all significantly higher in lesional HS skin than in healthy controls. IL-37 and IL-38 levels were significantly higher in perilesional HS skin than in healthy controls and were decreased in lesional HS skin. Limitations of the study are its descriptive nature and the small sample size. CONCLUSIONS: Our results showed a possible involvement of IL-36 cytokines in the inflammatory network of HS and a dysbalance between the agonistic and antagonistic cytokines in HS skin.

Climate Impacts From a Removal of Anthropogenic Aerosol Emissions.

Limiting global warming to 1.5 or 2.0°C requires strong mitigation of anthropogenic greenhouse gas (GHG) emissions. Concurrently, emissions of anthropogenic aerosols will decline, due to coemission with GHG, and measures to improve air quality. However, the combined climate effect of GHG and aerosol emissions over the industrial era is poorly constrained. Here we show the climate impacts from removing present-day anthropogenic aerosol emissions and compare them to the impacts from moderate GHG-dominated global warming. Removing aerosols induces a global mean surface heating of 0.5-1.1°C, and precipitation increase of 2.0-4.6%. Extreme weather indices also increase. We find a higher sensitivity of extreme events to aerosol reductions, per degree of surface warming, in particular over the major aerosol emission regions. Under near-term warming, we find that regional climate change will depend strongly on the balance between aerosol and GHG forcing.

Next-generation sequencing of the basal cell carcinoma miRNome and a description of novel microRNA candidates under neoadjuvant vismodegib therapy: an integrative molecular and surgical case study.

BACKGROUND: MicroRNAs (miRNAs) have been identified as key players in posttranscriptional gene regulation and have a significant impact on basal cell carcinoma (BCC) development. The Sonic hedgehog pathway inhibitor vismodegib has been approved for oral therapy of metastatic or advanced BCC. Here, a high-throughput miRNA sequencing analysis was carried out to identify differentially expressed miRNAs and possible novel miRNA candidates in vismodegib-treated BCC tissue. Additionally, we described our surgical experience with neoadjuvant oral vismodegib therapy. PATIENTS AND METHODS: A punch biopsy (4 mm) from a patient with an extensive cranial BCC under oral vismodegib therapy and a corresponding nonlesional epithelial skin biopsy were harvested. Total RNA was isolated, after which a sequencing cDNA library was prepared, and cluster generation was carried out, which was followed by an ultra-high-throughput miRNA sequencing analysis to indicate the read number of miRNA expression based on miRBase 21. In addition to the identification of differentially expressed miRNAs from RNA sequencing data, additional novel miRNA candidates were determined with a tool for identifying new miRNA sequences (miRDeep2). RESULTS: We identified 33 up-regulated miRNAs (fold change ≥2) and 39 potentially new miRNA candidates (miRDeep scores 0-43.6). A manual sequence analysis of the miRNA candidates on the genomic locus of chromosome 1 with provisional IDs of chr1_1913 and chr1_421 was further carried out and rated as promising (chr1_1913) and borderline (chr1_421). Histopathology revealed skip lesions in clinically healthy appearing skin at the tumor margins, which were the cause of seven re-excisions by micrographic controlled surgery to achieve tumor-free margins. CONCLUSION: miRNA sequencing revealed novel miRNA candidates that need to be further confirmed in functional Dicer knockout studies. Clinically, on the basis of our surgical experience described here, neoadjuvant vismodegib therapy in BCC appears to impede histopathologic evaluations with effects on surgical therapy. Thus, larger studies are necessary, but are not preferable at this time if other options are available.

BH3-only protein Bim predicts advanced stage of cutaneous melanoma.

BACKGROUND: Bim having strong pro-apoptotic effects belongs to the BH3-only proteins of the Bcl-2 protein family and contributes to survival pathways in cancer cells. OBJECTIVES: We aimed to investigate Bim protein expression in cutaneous melanoma (CM). METHODS: Bim protein expression was assessed by immunohistochemistry in primary and metastatic melanomas and correlated with clinical and histopathological features. RESULTS: The Bim immunoreactivity score of the primary melanomas investigated (4.6 ± 1.5) was significantly (P < 0.0001) higher than that observed in metastases (2.8 ± 1.1). Low Bim expression was significantly associated with primary nodular melanoma type (P = 0.005). Moreover, Bim expression was significantly inversely correlated with tumour thickness (r = -0.36; P = 0.0035), advanced stage of disease (stage III and IV; r = -0.60; P < 0.0001), disease relapse (r = -0.18; P = 0.034) and disease-related death (r = -0.19; P = 0.026). Advanced stage of disease was independently predicted by low Bim expression (P = 0.0010, odds ratio: 0.22, 95% CI: 0.10-0.56) on multivariate analysis; however, Bim was not shown to be an independent predictor for disease relapse (P = 0.40) and disease-related death (P = 0.77). CONCLUSIONS: Our data demonstrate that Bim protein expression is significantly inversely correlated with melanoma features that are associated with worse prognosis. We have shown that Bim protein expression in CM is an independent predictor for advanced disease confirming that this pro-apoptotic BH3-only protein might be a potent biomarker and promising therapeutic target.

Stress-coping styles of 459 emergency care physicians in Germany : A pilot study.

AIM: In addition to assessing stress-coping strategies in patients, equal attention should be paid to health-care professionals. The literature on the stress-coping strategies of emergency physicians - health-care professionals who are frequently subject to stress in a fast-paced clinical setting - is scant. Therefore, we aimed to investigate the stress-coping strategies of emergency-care physicians (ECPs) in Germany. METHODS: We conducted a cross-sectional study by approaching German Associations of Emergency Medicine Physicians and the two largest ECP recruitment agencies in Germany to invite their members to participate. We used the German Stress Coping Strategies Inventory ("Stressverarbeitungsfragebogen" SVF-78) to generate stress-coping scores that would cover both positive and negative strategies. Differences according to sex were also examined. Analyses including chi-square test, t test, and multinomial logistic regression modeling were performed. RESULTS: A total of 459 German ECPs were included in the study. Compared with men, women tended to have negative coping strategies (beta = 1.77, p < 0.001). Specifically, women tended to use social support (beta = 1.55, p = 0.002), avoidance (beta = 2.59, p < 0.001), escape (beta = 1.39, p = 0.004), rumination (beta = 1.58, p < 0.001), and resignation (beta = 2.09, p < 0.001), while being less likely than men to rely on minimization and denial of guilt. CONCLUSION: ECPs experience stress in the same manner as patients and other professionals, and they must address and cope with stress appropriately. For future research, studies with a longitudinal approach to monitor the underlying mechanisms are suggested. For clinical practice and policy-making, structural changes in work patterns and psychological support should be considered, which may be of particular benefit for female ECPs.

Comparison of lipidocolloid and chlorhexidine-impregnated tulle gras dressings following microscopically controlled surgery.

OBJECTIVE: Modified microscopically controlled surgery (MCS) is a staged and margin-controlled excision; after MCS, the selection of an appropriate initial wound dressing plays an important role in wound healing. A wide range of dressings is available for temporary wound coverage; however, data comparing different types of wound dressings after MCS are lacking. The aim of this study was to compare two commonly used and commercially available types of wound dressings. METHOD: We assessed pain levels, wound adherence, bleeding upon dressing removal and signs of infection, with chlorhexidine-impregnated tulle gras and a lipidocolloid dressing used for primary wound dressing following MCS. RESULTS: A total of 42 patients were included. Adherence of the dressing to the wound (p<0.001) and bleeding after removal (p=0.001) were significantly higher in the chlorhexidine-impregnated tulle gras dressing group. Pain during removal of wound dressing had a higher visual analogue scale score (1.9 ± 2.2) in the chlorhexidine-impregnated tulle gras dressing group compared to 0.7 ± 1.0 in the lipidocolloid dressing group (p=0.022). CONCLUSION: The results indicate that the lipidocolloid dressing, when compared with the chlorhexidine-impregnated tulle gras dressing, offers a significant benefit during removal in terms of less pain, less wound adherence and less wound bleeding. DECLARATION OF INTEREST: The authors have no conflict of interest to declare.

Histopathological correlates of basal cell carcinoma in the slice and en face imaging modes of high-definition optical coherence tomography.

BACKGROUND: High-definition optical coherence tomography (HD-OCT) scanners have recently been developed, providing significantly higher resolution than conventional OCT. OBJECTIVES: To assess the relationship between recently defined histopathological HD-OCT correlates of basal cell carcinomas (BCC) and possible predictors for the most common tumour subtypes. METHODS: For HD-OCT imaging, we used the Skintell(®) device. Twenty-five BCCs were histopathologically confirmed (including both vertical and horizontal haematoxylin and eosin and Alcian blue sectioning) and correlated with HD-OCT images. RESULTS: In the en face mode, lobulated nodules were seen in 21/25 BCCs (84%), peripheral rimming in 18/25 (72%), epidermal disarray in 18/25 (72%) and variably refractile stroma in 22/25 (88%). In the slice imaging mode, we observed destruction of layering in 19/25 (76%) BCCs. In both the slice and en face modes a significant correlation was observed between peritumoral rimming and grey/dark oval structures and lobulated nodules. Alcian blue stains showed peritumoral mucin deposits correlating with peripheral rimming around the tumour nodules. In a logistic regression model, we did not observe significant independent micromorphological HD-OCT predictors for either the solid or superficial BCC subtypes. CONCLUSIONS: In agreement with recent studies we have demonstrated that HD-OCT using the slice and en face imaging modes can visualize histopathological correlates of BCC, and potentially aid noninvasive diagnostics. However, using HD-OCT correlation it was not possible to predict the superficial or solid BCC subtypes. For the first time we have shown that peripheral rimming in HD-OCT correlates with peritumoral mucin deposition.

Expression of microRNAs in basal cell carcinoma.

BACKGROUND: Perturbations in the expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers. Differentially expressed miRNAs have not been systematically evaluated in basal cell carcinoma (BCC) of the skin. OBJECTIVES: To initiate a microarray-based miRNA profiling study to identify specific miRNA candidates that are differentially expressed in BCC. METHODS: Patients with BCC (n = 7) were included in this study. Punch biopsies were harvested from the tumour centre (lesional, n = 7) and from adjacent nonlesional skin (intraindividual control, n = 7). Microarray-based miRNA expression profiles were obtained on an Agilent platform using miRBase 16 screening for 1205 Homo sapiens (hsa)-miRNA candidates. To validate the microarray data, the expression of seven dysregulated miRNAs was measured by TaqMan quantitative real-time reverse transcription polymerase chain reaction. RESULTS: We identified 16 significantly upregulated (hsa-miR-17, hsa-miR-18a, hsa-miR-18b, hsa-miR-19b, hsa-miR-19b-1*, hsa-miR-93, hsa-miR-106b, hsa-miR-125a-5p, hsa-miR-130a, hsa-miR-181c, hsa-miR-181c*, hsa-miR-181d, hsa-miR-182, hsa-miR-455-3p, hsa-miR-455-5p and hsa-miR-542-5p) and 10 significantly downregulated (hsa-miR-29c, hsa-miR-29c*, hsa-miR-139-5p, hsa-miR-140-3p, hsa-miR-145, hsa-miR-378, hsa-miR-572, hsa-miR-638, hsa-miR-2861 and hsa-miR-3196) miRNAs in BCC compared with nonlesional skin. Data mining revealed connections to many tumour-promoting pathways, such as the Hedgehog and the mitogen-activated protein kinase/extracellular signal-regulated kinase signalling cascades. CONCLUSIONS: This study identified several miRNA candidates that may play a role in the molecular pathogenesis of BCC.

Induction of fat cell necrosis in human fat tissue after treatment with phosphatidylcholine and deoxycholate.

BACKGROUND: Injections with phosphatidylcholine- and deoxycholate-containing substances are used to treat localized fat accumulation and lipomas. It is believed that the injected substances induce fat cell destruction with subsequent acute panniculitis followed by a repair process of the treated fat tissue. OBJECTIVES: We investigated whether necrosis or apoptosis of fat cells was induced by the injected substances. METHODS: Samples of fat tissue of lipoma were collected at various times after injection and evaluated by light and electron microscopy, by immunostaining for active caspase-3 and antideoxyribonuclease I, in situ end-labelling (TUNEL staining), and biochemical caspase-3 assays. RESULTS: Light and electron microscopy showed fat cell necrosis in all areas of the treated lipomas. Low levels of active caspase-3 indicated the absence of apoptosis. CONCLUSIONS: Injection of the lipolytic substances phosphatidylcholine and deoxycholate leads to fat cell necrosis rather than apoptosis. However, additional studies evaluating different dosing and further time points after treatment are necessary.

In situ experimental evidence of the fate of a phytodetritus pulse at the abyssal sea floor.

More than 50% of the Earth' s surface is sea floor below 3,000 m of water. Most of this major reservoir in the global carbon cycle and final repository for anthropogenic wastes is characterized by severe food limitation. Phytodetritus is the major food source for abyssal benthic communities, and a large fraction of the annual food load can arrive in pulses within a few days. Owing to logistical constraints, the available data concerning the fate of such a pulse are scattered and often contradictory, hampering global carbon modelling and anthropogenic impact assessments. We quantified (over a period of 2.5 to 23 days) the response of an abyssal benthic community to a phytodetritus pulse, on the basis of 11 in situ experiments. Here we report that, in contrast to previous hypotheses, the sediment community oxygen consumption doubled immediately, and that macrofauna were very important for initial carbon degradation. The retarded response of bacteria and Foraminifera, the restriction of microbial carbon degradation to the sediment surface, and the low total carbon turnover distinguish abyssal from continental-slope 'deep-sea' sediments.

Laser Doppler scanning study of axillary skin before and after liposuction curettage in patients with focal hyperhidrosis.

BACKGROUND: Minimally invasive surgeries are frequently used in patients suffering from focal axillary hyperhidrosis (FAH). Sweat glands are removed surgically and the axillary skin is thinned out, with skin necrosis being a possible complication due to reduced microcirculation. Although of considerable interest, studies evaluating pre- and postoperative skin perfusion are unavailable. OBJECTIVE: To evaluate the blood flow of axillary skin in patients with severe focal axillary hyperhidrosis before and after liposuction curettage (LC). MATERIAL AND METHODS: The blood flow in the axillary skin of 11 patients was measured by laser Doppler perfusion imaging before surgery and on days 1, 7 and 28 after LC with a rasping cannula. Skin perfusion was measured in arbitrary units (AU) with measuring points in the axillary center (AC), the operated skin 2 cm from the center (2C) and the surrounding healthy skin (HS). RESULTS: No significant differences of preoperative skin perfusion were found (AC: 0.39 +/- 0.08 AU/2C: 0.38 +/- 0.07 AU/HS: 0.39 +/- 0.07 AU; p > 0.05). On the first and seventh postoperative days, AC (0.2 +/- 0.04 AU/0.27 +/- 0.81 AU) and 2C (0.2 +/- 0.03 AU/0.28 +/- 0.06 AU) area were significantly less perfused, whereas the HS showed higher perfusion values (0.59 +/- 0.1 AU/0.53 +/- 0.09 AU). Twenty-eight days after LC the 2C (0.36 +/- 0.07 AU) and HS (0.4 +/- 0.06 AU) skin revealed no significant differences compared to preoperative skin perfusion (p > 0.05). The AC perfusion was still slightly reduced (0.37 +/- 0.09 AU) without significant difference compared to preoperative findings. CONCLUSION: LC reduces the axillary skin blood flow with the axillary center being the least perfused area. However, in our collective, no correlation to possible side effects was observed.

HIV-associated facial lipoatrophy--review of current therapy options.

Highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy for HIV-infected patients. Long-term complications of both HIV-infection and antiretroviral agents are therefore of increasing concern. Facial lipoatrophy (FLA) is a stigmatizing complication associated with sever social impact and a reduced quality of life for the patient. - We aimed to review the treatment options of HIV-associated FLA. The current treatments available for treating FLA are limited and can be classified in three main categories: I. Medial therapy, II. Injectables with different duration of effect, and III. Surgical treatment options. Medical therapy can provide a small benefit but improvement is, at best, slow and partial. Injectables can yield marked results but are costly, time consuming and may be associated with complications such as granuloma formation. Surgical options such as augmentation with specially designed silicone implants may be of benefit for severe cases of FLA, however, they are associated with higher surgical complications and do not account for the dynamic process of FLA. - To summarize, until today no ideal strategies for treatment of HIV-associated FLA are available, and new therapies are strongly required. heart disease.

Validation of optical coherence tomography in vivo using cryostat histology.

We aimed to validate for the first time optical coherence tomography (OCT) measurements of epidermal thickness (ET) using cryopreparation for histology. OCT assessments of ET were performed on healthy skin using the algorithms as follows: first, peak-to-valley analysis of the A-scan (ET-OCT-V), second, line-traced image analysis of the B-scan (ET-OCT-IA). Histology was performed using cryostat sections which were also evaluated using the image analysis (ET-Histo). We selected 114 samples, including B-scans and corresponding histology, for method comparison between ET-OCT-IA and ET-Histo. Forty-two A-scans were available for method comparison between ET-OCT-V and ET-Histo. Bland and Altman plots revealed a marked bias with wide 95% limits of agreement for ET-OCT-V versus ET-Histo. Comparison of ET-OCT-IA versus ET-Histo revealed only a slight bias and narrow 95% limits of agreement. A-scan analysis for ET determination is linked to significant limitations and lacks agreement with histology. By contrast, we observed satisfactory agreement between ET-OCT-IA and ET-Histo indicating that both methods can be utilized interchangeably. OCT using the line-traced image analysis of the B-scan appears to be a valid and relatively practicable method for the determination of ET in vivo. Furthermore, the comparisons with the in vivo OCT profiles demonstrate that cryostat sectioning provides a better preservation of relative and absolute dimensions of skin layers than paraffin embedding.

Bilateral cheek-to-nose advancement flap: an alternative to the paramedian forehead flap for reconstruction of the nose.

Skin cancer on the nose is commonly treated with surgical excision resulting in defects that require closure. The surgeon is faced with many reconstructive options. The paramedian forehead flap is one commonly used technique. In this study we describe the bilateral cheek-to-nose advancement flap as an alternative to the paramedian forehead flap in patients with strong nasolabial folds and prominent cheek tissue laxity, who require closure of MOHS surgery defects on the nasal dorsum and sidewall. Twelve patients were treated with the latter flap and evaluated after 2 weeks and 6 months. The patients' subjective and the surgeons' objective evaluation after 6 months were either completely satisfied or satisfied. The bilateral cheek-to-nose advancement flap is a reliable tool in the interventional portfolio of the reconstructive surgeon.

The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions.

Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction. Expression levels of all investigated components were significantly lower in lesional HS skin (n = 18) compared to healthy controls (n = 10). TRBP1, PACT, AGO1, AGO2, and SND1 expression levels were significantly down-regulated in lesional HS skin compared to healthy-appearing perilesional skin (n = 7). TRBP2 and SND1 expression levels were significantly lower in healthy-appearing perilesional skin compared to healthy controls. In lesional HS skin, expression levels of PACT, AGO1, and AGO2 were significantly lower compared to psoriatic skin (n = 10). In summary, our data showed that all investigated components of RISC are dysregulated in the skin of HS patients, providing support for the hypothesis that miRNAs may have a pathological role in the inflammatory pathogenesis of HS.

Expression of miRNA-155, miRNA-223, miRNA-31, miRNA-21, miRNA-125b, and miRNA-146a in the Inflammatory Pathway of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) has been associated with marked inflammatory perturbation. The mechanisms regulating the inflammatory network remain elusive. microRNAs (miRNAs) have been described as gene regulators of inflammation. We evaluated the messenger RNA (mRNA) expression levels of six selected inflammation-related miRNAs in lesional and perilesional skin samples of HS patients and in healthy controls. Samples of 15 HS patients and 10 healthy controls were included in this prospective study. Expression levels of the miRNAs miRNA-155-5p, miRNA-223-5p, miRNA-31-5p, miRNA-21-5p, miRNA-125b-5p, and miRNA-146a-5p were studied by quantitative real-time reverse transcription polymerase chain reaction. We observed a significant overexpression of miRNA-155-5p, miRNA-223-5p, miRNA-31-5p, miRNA-21-5p, and miRNA-146a-5p in lesional HS skin compared to healthy controls. Expression of these miRNAs was also significantly increased in lesional HS skin when compared to perilesional skin. Only miRNA-155-5p showed an increased expression in perilesional skin compared to healthy controls. In contrast, miRNA-125b-5p had a significantly lower expression in lesional HS skin compared to perilesional skin. We found that the studied inflammation-related miRNAs were significantly dysregulated in lesional HS skin and may have regulatory roles in the inflammatory process of HS. Given their predicted targets and functions, our findings point to these miRNAs as potential disease biomarkers, and manipulation might be used therapeutically to target the inflammatory pathway in HS.