scholarly journals Expression of miR-135b in Psoriatic Skin and Its Association with Disease Improvement

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1603 ◽  
Author(s):  
Pablo Chicharro ◽  
Pedro Rodríguez-Jiménez ◽  
Mar Llamas-Velasco ◽  
Nuria Montes ◽  
Ancor Sanz-García ◽  
...  
Keyword(s):  
Severity Index ◽  
Psoriatic Skin ◽  
Local Inflammatory Response ◽  
Lesional Skin ◽  
Basal Expression ◽  
Severity Index Score ◽  
Residual Lesions ◽  
Generation Sequencing ◽  
Additional Sample ◽  
Skin Samples

miRNAs have been associated with psoriasis since just over a decade. However, we are far from a complete understanding of their role during the development of this disease. Our objective was to characterize the cutaneous expression of miRNAs not previously described in psoriasis, the changes induced following the treatment with biologicals and their association with disease improvement. Next generation sequencing was performed from five skin samples from psoriasis patients (lesional and non-lesional skin) and five controls, and from this cohort, 12 microRNAs were selected to be analyzed in skin samples from 44 patients with plaque psoriasis. In 15 patients, an additional sample was obtained after three months of biological treatment. MiR-9-5p, miR-133a-3p and miR-375 were downregulated in the lesional skin of psoriasis patients. After treatment, expression of miR-133a-3p, miR-375, miR-378a and miR-135b in residual lesions returned towards the levels observed in non-lesional skin. The decrease in miR-135b levels after treatment with biologics was associated with both the improvement of patients evaluated through Psoriasis Area and Severity Index score and the decrease in local inflammatory response. Moreover, basal expression of miR-135b along with age was associated with the improvement of psoriasis, suggesting its possible usefulness as a prognostic biomarker.

scholarly journals The effect of apremilast therapy on skin cytokine levels in patients with psoriasis

2020 ◽  
Vol 9 (3) ◽  
Author(s):  
Alexey A. Kubanov ◽  
Viktoria S. Solomka ◽  
Arfenya E. Karamova ◽  
Dmitry A. Verbenko ◽  
Elena L. Vasileva ◽  
...  
Keyword(s):  
Objective Assessment ◽  
Severity Index ◽  
Cd40 Ligand ◽  
Soluble Cd40 Ligand ◽  
Lesional Skin ◽  
Suspension Array ◽  
Phosphodiesterase 4 ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Skin Samples

Objective — Assessment of phosphodiesterase-4 inhibitor (apremilast) therapy’s influence on skin cytokine levels in patients with moderate-to-severe and severe psoriasis. Material and Methods — An open, uncontrolled study was conducted. 16 patients with plaque psoriasis (13 men, 3 women; mean ± standard deviation (SD) age 35.1±9.7 years, range 21-60) were enrolled. The mean Psoriasis Area and Severity Index (PASI) was 20.7±8.93 (range 10-47). All patients were prescribed apremilast 30 milligrams (mg) per os (PO) Bis In Die (BID). The efficacy of therapy was evaluated by PASI at 14 and 26 weeks of therapy. Lesional skin samples were collected at baseline and weeks 14 and 26. Levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL -33, interferon (INF)-γ, Soluble CD40-ligand (sCD40L), tumor necrosis factor (TNF)-α were measured by microsphere-based suspension array technology (Luminex® xMAP™ system). Results — Levels of cytokines (except IL-4 and IL-33) in lesional skin samples were found to have decreased at week 14 compared with those at baseline. Similar decreases were seen for IL-23, IL-25, IL-31, sCD40L at week 26. In contrast, the levels of other cytokines increased again at week 26, in comparison with baseline. Levels of IL-4 and IL-33 rose throughout the follow-up period. Cytokine levels in lesional skin samples were compared with those of healthy controls both at baseline and during therapy. Conclusion — The results of our study show that administering apremilast therapy to patients with psoriasis can bring the levels of cytokines involved in the IL-23/IL-17 axis in the lesional skin to the level of cytokine in non-lesional skin and to the levels in the skin of healthy individuals.

MicroRNA-125a Correlates with Decreased Psoriasis Severity and Inflammation and Represses Keratinocyte Proliferation

Dermatology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Fang Su ◽  
Liang Jin ◽  
Wei Liu
Keyword(s):  
Severity Index ◽  
Skin Tissue ◽  
Hacat Cells ◽  
Tissue Samples ◽  
Keratinocyte Proliferation ◽  
Lesional Skin ◽  
High Area ◽  
Tnf Α ◽  
Severity Index Score ◽  
Factor Α

Background: Psoriasis has a complex etiology related to inflammation and dysregulated immune system. MicroRNA (miR)-125a is a miRNA intimately related to inflammation and immunity; therefore, we presumed that it might play a role in the pathogenesis of psoriasis. This study aimed to investigate the correlation of miR-125a with disease severity and inflammation in psoriasis patients, and the effect of miR-125a on proliferation, apoptosis as well as its target signaling pathway in keratinocytes. Methods: Sixty psoriasis patients were consecutively recruited, then lesional and non-lesional skin tissue samples were collected. miR-125a in lesional and non-lesional skin tissues, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 mRNA expressions in lesional skin tissues were detected. Then, miR-125a overexpression, control overexpression, miR-125a knockdown and control knockdown plasmids were transfected into HaCaT cells. Subsequently, cell proliferation, apoptosis, IL-23R, JAK2, and STAT3 expressions were assessed. Results: miR-125a was reduced in lesional skin tissue compared with non-lesional skin tissue (p < 0.001), and it distinguished lesional skin tissue from non-lesional skin tissue with a high area under curve of 0.917 (95% CI 0.866–0.968). Negative association of miR-125a in lesional skin tissue with lesional body surface area (p = 0.037) and psoriasis area and severity index score (p < 0.001) was found. Additionally, miR-125a was negatively correlated with TNF-α (p = 0.001), IL-1β (p = 0.014), and IL-17 (p = 0.003) in lesional skin tissue. In cellular experiments, miR-125a overexpression inhibited proliferation and promoted apoptosis, while miR-125a knockdown enhanced proliferation and repressed apoptosis in HaCaT cells. Additionally, miR-125a negatively regulated the IL-23R/JAK2/STAT3 pathway in HaCaT cells. Conclusion: miR-125a could facilitate the disease monitoring and probably has the potential to be a therapeutic target in psoriasis.

Identifying Top Predictors of Change in Noncalcified Coronary Burden in Psoriasis by Machine Learning Over 1-Year

2021 ◽  
pp. 247553032110007
Author(s):  
Eric Munger ◽  
Amit K. Dey ◽  
Justin Rodante ◽  
Martin P. Playford ◽  
Alexander V. Sorokin ◽  
...  
Keyword(s):  
Machine Learning ◽  
Blood Pressure ◽  
Blood Cell ◽  
Cell Count ◽  
White Blood Cell Count ◽  
White Blood Cell ◽  
Severity Index ◽  
Blood Cell Count ◽  
Psoriasis Area Severity Index ◽  
Severity Index Score

Background: Psoriasis is associated with accelerated non-calcified coronary plaque burden (NCB) by coronary computed tomography angiography (CCTA). Machine learning (ML) algorithms have been shown to effectively identify cardiometabolic variables with NCB in cross-sectional analysis. Objective: To use ML methods to characterize important predictors of change in NCB by CCTA in psoriasis over 1-year of observation. Methods: The analysis included 182 consecutive patients with 80 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative, a prospective, observational cohort study at baseline and 1-year using the random forest regression algorithm. NCB was assessed at baseline and 1-year from CCTA. Results: Using ML, we identified variables of high importance in the context of predicting changes in NCB. For the cohort that worsened NCB (n = 102), top baseline variables were cholesterol (total and HDL), white blood cell count, psoriasis area severity index score, and diastolic blood pressure. Top predictors of 1-year change were change in visceral adiposity, white blood cell count, total cholesterol, c-reactive protein, and absolute lymphocyte count. For the cohort that improved NCB (n = 80), the top baseline variables were HDL cholesterol related including apolipoprotein A1, basophil count, and psoriasis area severity index score, and top predictors of 1-year change were change in apoA, apoB, and systolic blood pressure. Conclusion: ML methods ranked predictors of progression and regression of NCB in psoriasis over 1 year providing strong evidence to focus on treating LDL, blood pressure, and obesity; as well as the importance of controlling cutaneous disease in psoriasis.

scholarly journals Confocal laser endomicroscopy reveals alterations in duodenal permeability in patients with acute pancreatitis

2019 ◽  
Vol 47 (3) ◽  
pp. 1279-1287
Author(s):  
Lingjia Sun ◽  
Min Yue ◽  
Yining Dai ◽  
Chaohui Yu ◽  
Chunxiao Chen
Keyword(s):  
Acute Pancreatitis ◽  
Large Scale ◽  
Duodenal Bulb ◽  
Severity Index ◽  
Duodenal Mucosa ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Mucosal Permeability ◽  
Reactive Protein ◽  
Severity Index Score

Objective Intestinal permeability increases during the course of acute pancreatitis (AP). We assessed duodenal permeability alterations in patients with AP by confocal laser endomicroscopy (CLE). Methods Thirty patients with AP underwent CLE evaluation of the antral and duodenal mucosa. Images were graded based on the appearance of capillaries and the degree of fluorescein leakage. Results Patients with AP had increased duodenal mucosal permeability that could be detected by CLE. The mucosal permeability progressively increased in the gastric antrum, duodenal bulb, and descending duodenum. The CLE parameters in the antrum and duodenal bulb were not significantly different between patients with mild and severe AP. The CLE grades in the descending duodenum were higher in patients with severe than mild AP. The C-reactive protein level in AP was positively correlated with the permeability in the duodenal bulb and descending duodenum, while the computed tomography severity index score was positively correlated with the mucosal permeability in the duodenal bulb and descending duodenum. Conclusion CLE revealed increased duodenal permeability in patients with AP. Higher permeability in the descending duodenum was observed in severe than mild AP. Further large-scale studies are needed to confirm the relationship between altered duodenal permeability and the severity of AP.

scholarly journals The Safety and Efficacy of Pregabalin Add-on Therapy in Restless Legs Syndrome Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Hyoeun Bae ◽  
Yong Won Cho ◽  
Keun Tae Kim ◽  
Richard P. Allen ◽  
Christopher J. Earley
Keyword(s):  
Side Effects ◽  
Restless Legs Syndrome ◽  
Severity Index ◽  
Efficacy And Safety ◽  
Restless Legs ◽  
Persistent Symptoms ◽  
Before And After ◽  
Severity Index Score ◽  
Irls Score ◽  
Symptomatic Control

Pregabalin is increasingly being used as a first-line treatment for symptomatic control of restless legs syndrome (RLS). This study aimed to evaluate the efficacy and safety of pregabalin as add-on therapy in RLS patients already taking dopamine agonists (DA) but still in need of further management. Patients with idiopathic RLS were enrolled, and all had already been prescribed DA for at least 3 months but still had either persistent symptoms, side effects, or comorbid insomnia. An initial dose of 75 mg pregabalin was begun, adjusted as needed, and maintained at a stable dose for 4 weeks, followed by observation for a total of 8 weeks. RLS symptoms and insomnia scores were evaluated before and after add-on pregabalin treatment. Patients were monitored for side effects that could be attributed to pregabalin. A total of 32 RLS patients were enrolled, and 20 subjects remained until the endpoint. After the pregabalin add-on, the mean IRLS score showed significant improvement compared to the baseline (p &lt; 0.001). The insomnia severity index score also improved (p = 0.036), and no serious adverse effects were observed. Our preliminary data suggests the potential for pregabalin as an add-on therapy to DA with regards to both efficacy and safety in patients who have inadequate RLS improvement.

scholarly journals LC-MS/MS analysis of lesional and normally looking psoriatic skin reveals significant changes in protein metabolism and RNA processing

2020 ◽  
Author(s):  
V.V. Sobolev ◽  
R.H. Ziganshin ◽  
A.V. Mezentsev ◽  
A.G. Soboleva ◽  
M. Denieva ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Rna Processing ◽  
Protein Identification ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Psoriatic Skin ◽  
Differentially Expressed Proteins ◽  
Kinin System ◽  
Lesional Skin ◽  
Kallikrein Kinin System

AbstractBackgroundPlaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available.AimThe aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease.MethodsSkin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients’ skin compared to skin of the healthy volunteers.ResultsThe performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. We discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG in normally looking skin of the patients. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes.ConclusionOur findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease. Data are available via ProteomeXchange with identifier PXD021673.

scholarly journals Multiple Brain Abscesses due toStreptococcus anginosus: Prediction of Mortality by an Imaging Severity Index Score

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
K. O. Kragha
Keyword(s):  
Elderly Patient ◽  
Prognostic Value ◽  
Severity Index ◽  
Altered Mental Status ◽  
Index Score ◽  
Aggressive Treatment ◽  
Streptococcus Anginosus ◽  
Prediction Of Mortality ◽  
Severity Index Score ◽  
Brain Abscesses

An elderly patient with altered mental status, brain abscesses, ventriculitis, and empyemas died of septic shock and brain abscesses secondary toStreptococcus anginosusdespite aggressive treatment. An imaging severity index score with a better prognostic value than the Glasgow coma scale predicted mortality in this patient.

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