Expression Signature of Immune-Related MicroRNAs in Autoimmune Skin Disease: Psoriasis and Vitiligo Insights.

BACKGROUND: Psoriasis and vitiligo are both chronic, skin-specific diseases classified as autoimmune diseases due to the involvement of several biochemical pathways in their pathogenesis, similar to those altered in other autoimmune diseases. The role of miRNAs in regulating skin autoimmune function has yet to be fully characterized. AIM: The aim of this study was to assess the expression profile of a panel of 11 circulating immune-related miRNAs in patients with autoimmune skin diseases, specifically psoriasis and vitiligo, and correlate their expression signature with the clinicopathological features of the diseases. SUBJECTS AND METHODS: Relative gene expression quantification for 11 immune-related circulating miRNAs in plasma was done for 300 subjects-100 patients with psoriasis, 100 patients with vitiligo and 100 normal healthy volunteers-followed by different modalities of bioinformatics analysis for the results. RESULTS: The expression levels of all the studied immune-related miRNAs were elevated in both autoimmune skin disorders, with much higher levels of expression in psoriasis than in vitiligo patients. There was a significant correlation between most of the studied miRNAs, suggesting shared target genes and/or pathways. Moreover, all the studied miRNAs showed significant results as biomarkers for autoimmune skin disease, with miRNA-145 being the best candidate. Regarding the clinicopathological data, miRNA-7, miRNA-9, miRNA-145, miRNA-148a, and miRNA-148b were positively correlated with age. All the miRNAs were inversely correlated with obesity and disease duration. CONCLUSION: This study highlights the critical role of miRNAs in skin-specific autoimmune diseases that proved to be potential biomarkers for autoimmune skin disorders, warranting their exploration as therapeutic targets.

Mannose-binding lectin gene polymorphism in psoriasis and vitiligo: an observational study and computational analysis.

Introduction: Psoriasis and vitiligo are inflammatory autoimmune skin disorders with remarkable genetic involvement. Mannose-binding lectin (MBL) represents a significant immune molecule with one of its gene variants strongly linked to autoimmune diseases. Therefore, in this study, we investigated the role of the MBL variant, rs1800450, in psoriasis and vitiligo disease susceptibility. Methods: The study comprised performing in silico analysis, performing an observational study regarding psoriasis patients, and performing an observational study regarding vitiligo patients. Various in silico tools were used to investigate the impact of the selected mutation on the function, stability, post-translational modifications (PTMs), and secondary structures of the protein. In addition, a total of 489 subjects were enrolled in this study, including their demographic and clinicopathological data. Genotyping analysis was performed using real-time PCR for the single nucleotide polymorphism (SNP) rs1800450 on codon 54 of the MBL gene, utilizing TaqMan genotyping technology. In addition, implications of the studied variant on disease susceptibility and various clinicopathological data were analyzed. Results: Computational analysis demonstrated the anticipated effects of the mutation on MBL protein. Furthermore, regarding the observational studies, rs1800450 SNP on codon 54 displayed comparable results in our population relative to global frequencies reported via the 1,000 Genomes Project. This SNP showed no significant association with either psoriasis or vitiligo disease risk in all genetic association models. Furthermore, rs1800450 SNP did not significantly correlate with any of the demographic or clinicopathological features of both psoriasis and vitiligo. Discussion: Our findings highlighted that the rs1800450 SNP on the MBL2 gene has no role in the disease susceptibility to autoimmune skin diseases, such as psoriasis and vitiligo, among Egyptian patients. In addition, our analysis advocated the notion of the redundancy of MBL and revealed the lack of significant impact on both psoriasis and vitiligo disorders.

Circulating microRNA203 and its target genes' role in psoriasis pathogenesis.

Numerous microRNAs (miRNAs) have been found to have an aberrant expression in the peripheral blood or psoriasis patients' lesions. Psoriasis was shown to have the abnormal expression of microRNA-203 (miR-203). It is a skin-specific signal that governs cellular proliferation in a protein kinase C-dependent manner and is mostly generated by keratinocytes. This work evaluated the expression levels of the circulating miR-203 target genes SOCS3, SOCS6, TP63, TNF-, IL8, and IL24 in psoriasis patients. Using a relative quantitation PCR technique, we determined the expression levels of miR-203 and its target genes (SOCS3, SOCS6, TP63, TNF-, IL8, and IL24) in the plasma of 120 psoriatic patients and matched healthy controls. The disease characteristics of the patients were then correlated with the expression results. We also conducted numerous enrichment analyses for the diseases, functions, and pathways connected to the under-researched biomarkers. Compared to healthy controls, psoriatic patients had significantly increased levels of miR-203 expression; 7.1 (4.4-9.9). In contrast, psoriatic patients had significantly lower expression of all the examined genes compared to healthy controls. Regarding all the study biomarkers, the receiver operating characteristic (ROC) curve analysis demonstrated significant sensitivity and specificity for differentiating between psoriatic patients and healthy controls. According to the results of the disease matching score generated by miR-203 and its target genes, psoriasis was ranked first with a score of 4.45. The third-place finisher with a value of 3.98, it also demonstrated that miR-203 and its target genes are connected to various skin disorders. Our results show that miR-203 contributes to psoriasis pathogenesis not only locally in skin lesions but also in circulation, indicating that it may contribute to the systemic symptoms of the illness. MiR-203 overexpression in psoriasis suggests that miR-203 may be involved in an anti-inflammatory response because it targets both SOCS gene family members and pro-inflammatory cytokines.

Intralesional injection of purified protein derivative versus Candida antigen in treatment of genital warts.

The Genital warts are common sexually transmitted diseases caused by definite types of human papillomavirus. There are many strategies for the treatment of genital wart and intralesional immunotherapy is considered to be a safe and effective treatment modality. However, there are lack of studies that comparing the clinical effectiveness of intralesional purified protein derivative (PPD) and Candida antigen (CA) in genital wart treatment. To investigate the effectiveness and safety of PPD and CA in the treatment of genital warts. Eighty patients were enrolled in this study and were randomly divided into 2 groups with 40 patients in each. Each antigen was injected intralesionally at a dose of 0.1 ml into the largest wart every 2 weeks until complete improvement or for a maximum of four sessions. Complete clinical response was demonstrated in 65%, 62.5% in PPD and CA groups, respectively. There was no statistically difference between both groups. After the 3-month follow-up period, 72.5%, 85% of patients showed complete clearance in PPD and CA groups respectively. Side effects were mild and insignificant in both groups. Recurrence was observed in only one patient in each group. Immunotherapy by intralesional PPD and CA injection is considered to be effective and well-tolerated modalities in treatment of genital wart with minimal side effects and recurrence rate compared to other modalities.

Investigating melanogenesis-related microRNAs as disease biomarkers in vitiligo.

Vitiligo is considered a disabling disease that affects physical, social, psychological, and occupational aspects of an individual's quality of life. The search for non-invasive and reliable biomarkers for vitiligo's early diagnosis, prognosis, and treatment prediction is under intensive investigation. There is currently an emerging interest in employing miRNAs as biomarkers to predict vitiligo diagnosis and prognosis, inspired by the well-preserved nature of miRNAs in serum or plasma. In the current study, we assessed a panel of 20 melanogenesis pathway-related microRNAs (miRNAs) using quantitative real-time PCR technique in 85 non-segmental vitiligo (NSV) patients compared to 85 normal controls followed by function and pathway enrichment analysis for the miRNAs with significant results. Twelve out of the 20 circulating miRNAs showed significantly higher expression levels in vitiligo patients relative to controls where miR-423 show the highest expression level followed by miR-182, miR-106a, miR-23b, miR-9, miR-124, miR-130a, miR-203a, miR-181, miR-152, and miR-320a. While six miRNAs (miR-224, miR-148a, miR-137, and miR-7, miR-148b, miR-145, miR-374b, and miR-196b) didn't show significant expression level. The analysis of the receiver operating curve indicated that miR-423, miR-106a, and miR-182 were outstanding biomarkers with the highest areas under the curve in vitiligo. This study is the first Egyptian study to investigate a panel of miRNAs expression profile in the plasma of patients with NSV. Our results suggest that specific circulating miRNAs signature might be implicated in vitiligo pathogenesis and could potentially be used as biomarkers in vitiligo.

The lncRNA PRINS-miRNA-mRNA Axis Gene Expression Profile as a Circulating Biomarker Panel in Psoriasis.

BACKGROUND: The interaction between genes and the environment in psoriasis is firmly coupled by epigenetic modification. Epigenetic modifications are inherited variations in gene expression devoid of DNA sequence alterations. Non-coding RNAs are regarded as one of the epigenetic modifications that lead eventually to enduring heritable variations in gene expression. In the present study, we chose the lncRNA, Psoriasis-susceptibility-Related RNA Gene Induced by Stress (PRINS) known to have a regulatory role in psoriasis and deduced its axis of lncRNA-miRNA-mRNA through an in silico data analysis. We aimed to assess the expression levels of this lncRNA-miRNA-mRNA in patients with psoriasis to elucidate their possible roles in psoriasis management. METHODS: We investigated the lncRNA-PRINS and its target microRNAs (miRNA124-3p, miRNA203a-5p, miRNA129-5p, miRNA146a-5p, miRNA9-5p) and partner genes (NPM, G1P3) expression levels in the plasma of 120 patients with psoriasis compared to 120 healthy volunteers using quantitative real-time polymerase chain reaction and correlated the results with the patients' clinicopathological data. Finally, we performed a function, disease, and pathway enrichment analysis for the LncRNA-miRNA-mRNA axis under study. RESULTS: The lncRNA PRINS, G1P3, and NPM genes showed significantly under-expressed levels while all miRNAs included in the study showed significant over-expression in patients with psoriasis relative to controls. The lncRNA PRINS, G1P3, and NPM genes showed a significant direct correlation with each other and inverse significant correlations with all miRNAs under study. All the study biomarkers showed significant results for discriminating between patients with psoriasis and controls using a receiver operating curve analysis with sensitivity over 90% except for PRINS, which was 74.2%. The G1P3 gene showed a direct significant correlation with body mass index in patients with psoriasis (p = 0.009) and an inverse significant correlation with age (p = 0.034). The NPM gene showed a significant correlation with body mass index in patients with psoriasis (p = 0.002). CONCLUSIONS: Based on our results, we suggest that restoring the altered PRINS-miRNA-mRNA axis gene expression levels might represent a tool to prevent psoriasis worsening, along with standard therapy. Thus, on the clinical practice level, the PRINS-miRNA-mRNA axis expression profile can be utilized in designing specific targeted therapy aimed at applying a personalized medicine approach among patients with psoriasis.

PSORS1 Locus Genotyping Profile in Psoriasis: A Pilot Case-Control Study.

(1) Background: The psoriasis susceptibility 1 (PSORS1) locus, located within the major histocompatibility complex, is one of the main genetic determinants for psoriasis, the genotyping profile for three single-nucleotide polymorphisms (SNPs) comprising the PSORS1 locus: rs1062470 within PSORS1C1/CDSN genes, rs887466 within PSORS1C3 gene, rs10484554 within LOC105375015 gene, were investigated and correlated with psoriasis risk and severity. (2) Methods: This pilot case-controlled study involved 100 psoriatic patients and 100 healthy individuals. We investigated three SNPs and assessed the relative gene expression profile for the PSORS1C1 gene. We then correlated the results with both disease risk and severity. (3) Results: The most significantly associated SNP in PSORS1 locus with psoriasis was rs10484554 with its C/T genotype 5.63 times more likely to develop psoriasis under codominant comparison. Furthermore, C/T and T/T genotypes were 5 times more likely to develop psoriasis. The T allele was 3 times more likely to develop psoriasis under allelic comparison. The relative gene expression of PSORS1C1 for psoriatic patients showed to be under-expressed compared to normal controls. (4) Conclusions: Our study revealed the association of the three studied SNPs with psoriasis risk and severity in an Egyptian cohort, indicating that rs10484554 could be the major key player in the PSORS1 locus.

Acquired hemophilia A (AHA): underreported, underdiagnosed, undertreated medical condition.

BACKGROUND: Acquired hemophilia A (AHA) is a rare acquired bleeding disorder occurred due to the formation of inhibitory antibodies neutralizing endogenous factor VIII. MAIN BODY: About half the cases are idiopathic. Symptoms include severe and unexpected bleeding that could be life-threatening. High index of suspicion should be raised when unexplained subcutaneous or post-surgical bleeding with isolated prolonged APTT. CONCLUSIONS: Acquired hemophilia A is a rare underdiagnosed underreported acquired hemostatic disorder that presents with sudden usually life-threatening bleeding; it is crucial to raise awareness and suspicion index of clinicians for early diagnosis and treatment to avoid morbidity and mortality.

Split-face comparative study of fractional Er:YAG laser versus microneedling radiofrequency in treatment of atrophic acne scars, using optical coherence tomography for assessment.

BACKGROUND: Efficacy and safety of ablative fractional laser used for treatment of acne scars have been described in several studies. Recently, microneedling radiofrequency treatment has been showing promising results with low risk of side effects and rapid healing time. OBJECTIVE: To study efficacy and safety of ablative fractional Er:YAG laser 2940 nm and microneedling radiofrequency for facial atrophic acne scar. METHODS: 21 patients with atrophic postacne scars were randomized to MRF for one half of the face and laser for the other half. Four sessions were performed monthly. For evaluation, the validated scale "Quantitative Global Grading System for Postacne Scarring" and patient's satisfaction were used before and 3 months after treatment. Optical coherence tomography imaging of the skin was used as an objective tool for assessment. RESULTS: Both sides showed significant improvement on clinical evaluation with no significant difference. Optical coherence tomography assessment showed significant increase of both epidermal and dermal thickness compared to baseline. CONCLUSION: Both MRF and ablative fractional Er. YAG laser 2940 nm are effective in the treatment of post acne scars. Microneedling radiofrequency is better tolerated, with lower downtime and fewer side effects.

Assessment of changes in color and size of vitiligo lesions during treatment with narrow band ultraviolet B.

BACKGROUND: Many treatment modalities have been used to stabilize vitiligo and induce repigmentation. Several methods were used to monitor the color changes inside the treated lesions such as spectroscopes and colorimeters that measure the melanin index inside the lesion. OBJECTIVE: To study whether the colorimeter and point counting technique can be used as objective methods in monitoring vitiligo lesions during treatment with Nb-UVB. METHODS: Twenty randomly chosen patients with non-segmental vitiligo were enrolled in this interventional study. Vitiligo disease activity score was recorded in each patient. Patients received Nb-UVB three times per week for 6 months. Two lesions were chosen in each patient, and each lesion was assessed for size using point counting technique and degree of color using the Dermacatch® at the beginning of the treatment and evaluated for changes in color and size every 4 weeks till the end of the treatment. RESULTS: After 6 months of treatment, regarding the lesion size, 90% of lesions showed variable degrees of repigmentation and 10% showed increase in size, indicating increased activity of the disease, and regarding to color changes. We noticed that after one month of Nb-UVB treatment, there is marked increase in MI measurements in many lesions before any clinical improvement appeared, while at the end of treatment, inside the lesion; 95% showed an increase in melanin index and 5% showed no elevation. While the color changes outside the lesion showed 75% of lesions increased in melanin index, 15% remained unchanged and 10% of the lesions showed decrease in melanin index. CONCLUSION: Colorimeter was able to detect change in color after only one month of treatment before it was clinically apparent which means that it can be used as a prognostic tool.

Evaluating sentence representations for biomedical text: Methods and experimental results.

Text representations ar one of the main inputs to various Natural Language Processing (NLP) methods. Given the fast developmental pace of new sentence embedding methods, we argue that there is a need for a unified methodology to assess these different techniques in the biomedical domain. This work introduces a comprehensive evaluation of novel methods across ten medical classification tasks. The tasks cover a variety of BioNLP problems such as semantic similarity, question answering, citation sentiment analysis and others with binary and multi-class datasets. Our goal is to assess the transferability of different sentence representation schemes to the medical and clinical domain. Our analysis shows that embeddings based on Language Models which account for the context-dependent nature of words, usually outperform others in terms of performance. Nonetheless, there is no single embedding model that perfectly represents biomedical and clinical texts with consistent performance across all tasks. This illustrates the need for a more suitable bio-encoder. Our MedSentEval source code, pre-trained embeddings and examples have been made available on GitHub.

The SNPcurator: literature mining of enriched SNP-disease associations.

Database URL: http://snpcurator.science.uu.nl/.