Differential Expression and in Silico Functional Analysis of Plasma MicroRNAs in the Pathogenesis of Non-segmental Vitiligo.

Vitiligo is a disease characterized by acquired depigmentation, white macules, and patches on the skin due to the dysfunction of epidermal melanocytes. In this study, we attempt to profile the microRNA (miRNA) expression patterns and predict the potential targets, assessing the biological functions of differentially expressed miRNAs in the blood of generalized vitiligo patients. Peripheral blood samples were taken from all participants, and the expression levels of 89 identified miRNAs were analyzed with real-time quantitative polymerase chain reaction (PCR). The results indicated significant upregulation of six miRNAs and downregulation of 19 miRNAs in the plasma of vitiligo patients. The top three upregulated miRNAs were hsa-miR-451a, hsa-miR-25-3p, and hsa-miR-19a-3p, and the top three downregulated miRNAs were hsa-miR-146a-5p, hsa-miR-940, and hsa-miR-142-3p. Moreover, the miRNA expression profiles of patients with Type 3 and Type 4 phototypes were substantially different in such a way that the patients with Type 3 phototype would be more prone to the emergence of melanoma and cancer. While significant variations in the expression patterns of miRNAs in male and female vitiligo patients were demonstrated, miR-let-7i-5p, miR-19a-3p, miR-25-3p, and miR-451a were commonly upregulated, and miR-142-3p and miR-146a-5p were commonly repressed in both sexes. This study may shed light on the roles of differentially expressed miRNAs in vitiligo patients by examining the miRNA expression patterns and the combined effects of miRNA and their predicted targets.

Blood microRNA expressions in patients with mild to moderate psoriasis and the relationship between microRNAs and psoriasis activity

Abstract Background: In recent studies, microRNAs (mi-RNAs) have been shown to play an important role in psoriasis pathogenesis. However, studies evaluating mi-RNAs in the blood of psoriasis patients including a large number of mi-RNA panels are scarce. Objective: The authors aimed to assess mi-RNA expressions in blood samples of psoriasis patients, as well as to evaluate the association between mi-RNA expression and psoriasis severity. Methods: This was a case-control study on 52 patients with psoriasis vulgaris and 54 controls. Patients' medical history, psoriasis area and severity index (PASI) scores, and dermatology life quality index (DLQI) scores were recorded. The 42 disease-related mi-RNA primers were assessed by real-time PCR. Results: In the patient group, 13.4% presented nail involvement and 8.2% had psoriatic arthritis. The mean PASI and DLQI scores were 7.90 ± 8.83 and 8.13 ± 5.50, respectively. Among 42 mi-RNA primers; hsa-miR-155-5p, hsa-miR-369-3p, hsa-miR-193b-3p, hsa-miR-498, hsa-miR-1266-5p, hsa-let-7d-5p, hsa-miR-205-5p, hsa-let-7c-5p, hsa-miR-30b-3p, and hsa-miR-515-3p expressions were significantly up-regulated, whereas hsa-miR-21-5p, hsa-miR-142-3p, hsa-miR-424-5p, hsa-miR-223-3p, hsa-miR-26a-5p, hsa-miR-106b-5p, hsa-miR-126-5p, hsa-miR-181a-5p, hsa-miR-222-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-17-3p, hsa-miR-30b-5p, hsa-miR-130a-3p, hsa-miR-30e-5p, and hsa-miR-16-5p were significantly down-regulated in psoriasis patients when compared with the control group (p < 0.05). Study limitations: As the study included patients with mild to moderate psoriasis who mostly only received topical treatments, changes in miRNA before and after systemic treatments were not assessed. Conclusion: The detection of 24 mi-RNA expressions up- or down-regulated in psoriasis patients, even in those with milder disease, further supports the role of mi-RNAs in the psoriasis pathogenesis. Future studies should clarify whether mi-RNAs can be used as a marker for psoriasis prognosis or as a therapeutic agent in the treatment of psoriasis.

Blood microRNA expressions in patients with mild to moderate psoriasis and the relationship between microRNAs and psoriasis activity.

BACKGROUND: In recent studies, microRNAs (mi-RNAs) have been shown to play an important role in psoriasis pathogenesis. However, studies evaluating mi-RNAs in the blood of psoriasis patients including a large number of mi-RNA panels are scarce. OBJECTIVE: The authors aimed to assess mi-RNA expressions in blood samples of psoriasis patients, as well as to evaluate the association between mi-RNA expression and psoriasis severity. METHODS: This was a case-control study on 52 patients with psoriasis vulgaris and 54 controls. Patients' medical history, psoriasis area and severity index (PASI) scores, and dermatology life quality index (DLQI) scores were recorded. The 42 disease-related mi-RNA primers were assessed by real-time PCR. RESULTS: In the patient group, 13.4% presented nail involvement and 8.2% had psoriatic arthritis. The mean PASI and DLQI scores were 7.90±8.83 and 8.13±5.50, respectively. Among 42 mi-RNA primers; hsa-miR-155-5p, hsa-miR-369-3p, hsa-miR-193b-3p, hsa-miR-498, hsa-miR-1266-5p, hsa-let-7d-5p, hsa-miR-205-5p, hsa-let-7c-5p, hsa-miR-30b-3p, and hsa-miR-515-3p expressions were significantly up-regulated, whereas hsa-miR-21-5p, hsa-miR-142-3p, hsa-miR-424-5p, hsa-miR-223-3p, hsa-miR-26a-5p, hsa-miR-106b-5p, hsa-miR-126-5p, hsa-miR-181a-5p, hsa-miR-222-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-17-3p, hsa-miR-30b-5p, hsa-miR-130a-3p, hsa-miR-30e-5p, and hsa-miR-16-5p were significantly down-regulated in psoriasis patients when compared with the control group (p<0.05). STUDY LIMITATIONS: As the study included patients with mild to moderate psoriasis who mostly only received topical treatments, changes in miRNA before and after systemic treatments were not assessed. CONCLUSION: The detection of 24 mi-RNA expressions up- or down-regulated in psoriasis patients, even in those with milder disease, further supports the role of mi-RNAs in the psoriasis pathogenesis. Future studies should clarify whether mi-RNAs can be used as a marker for psoriasis prognosis or as a therapeutic agent in the treatment of psoriasis.

Plasma dermcidin levels in acne patients, and the effect of isotretinoin treatment on dermcidin levels.

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. Dermcidin (DCD) is an antimicrobial peptide released from eccrine sweat glands and sebaceous glands. Studies investigating the role of DCD expression in acne development are scarce. The aim of this study was to determine the relationship between DCD expression and acne vulgaris and the effect of oral isotretinoin treatment on DCD levels. Two groups (one patient group and one control group) were included in the study. The patient group consisted of 30 patients with acne vulgaris who were given oral isotretinoin treatment for 6 months until the cumulative dose was attained. Plasma DCD levels were investigated before and 6 months after treatment. The control group comprised 30 volunteer individuals without acne vulgaris or any inflammatory dermatosis. Of the patients, 24 (80%) had Grade 3, 3 (10%) had Grade 1, and 3 (10%) had Grade 4 acne vulgaris, as determined according to the Pillsbury scoring method. The DCD levels in the control group were significantly higher than those in pretreatment patients (39.53 ± 20.2 vs. 28.60 ± 20.12, p = .004). Additionally, pretreatment DCD levels were significantly increased after 6 months of isotretinoin treatment in the patient group (28.60 ± 20.12 vs. 35.07 ± 24.02, p = .012). The mean pretreatment global acne grading system score of 20.86 ± 4.43 was decreased to 5.17 ± 1.91 in patients after treatment (p < .001). This study indicated that DCD plays an important role in the pathogenesis of acne. It demonstrates anti-inflammatory properties in acne vulgaris. Moreover, it was shown that isotretinoin treatment may improve acne vulgaris by increasing DCD levels.

Evaluation of Erythroid Disturbance and Thiol-Disulphide Homeostasis in Patients with Psoriasis.

This study aims to assess how mean corpuscular volume (MCV), red cell distribution width (RDW), and thiol-disulphide homeostasis are altered in psoriasis patients. This is a cross-sectional review of 76 healthy volunteers and 87 psoriasis patients who were consecutively admitted to the department of dermatology. Psoriasis patients and healthy controls were statistically similar with respect to age, sex, body mass index, blood pressures, and disease duration (p > 0.05 for all). When compared to healthy controls, psoriasis patients had significantly higher MCV, RDW, C-reactive protein (CRP), disulphide, disulphide/native thiol, and disulphide/total thiol (p < 0.001 for all). However, psoriasis patients had significantly lower native thiol and native thiol/total thiol (p = 0.009 and p < 0.001, respectively). When compared to healthy controls, the patients with Psoriasis Area Severity Index (PASI) ≤ 10 and patients with PASI > 10 had significantly higher MCV, disulphide, disulphide/native thiol, and disulphide/total thiol (p < 0.001 for all). The patients with PASI ≤ 10 and patients with PASI > 10 had significantly lower native thiol/native thiol than healthy controls (p < 0.001 for all). The psoriasis patients with PASI > 10 had significantly higher RDW and CRP than healthy controls and patients with PASI ≤ 10 (p < 0.001 for all). Disulphide, disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol correlate significantly with both PASI scores and disease duration. Thiol-disulphide homeostasis is enhanced in psoriasis patients. Ongoing inflammation and increased oxidative stress in psoriasis patients also trigger the formation of prooxidants which are neutralized by antioxidants such as thiols. That is why plasma thiol levels are decreased in psoriasis patients.

The Role of Forkhead Box Class O3A and SIRT1 Gene Variants in Early-Onset Psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder, which is characterized by a heightened immunological response. Although the immunogenetics of this chronic inflammatory disorder is poorly understood, its expression is known to be dependent on proinflammatory cytokines. It is known that two distinct subtypes of chronic plaque psoriasis: Early-onset psoriasis (EOP) before the age of 40 years and late-onset psoriasis after the age of 40 years. Forkhead box class O3A (FOXO3A) is a transcription factor, which plays an important role in cell-cycle regulation, apoptosis, oxidative stress, and DNA repair. The silent information regulator (SIRT) is thought to have a role in skin disorders, including psoriasis, that are characterized by hyperproliferation and inflammation. AIM: The aim of this study was to investigate FOXO3A and SIRT1 gene polymorphisms in EOP. METHODS: The study group consisted of 142 EOP patients and 123 unrelated healthy controls. FOXO3A polymorphisms were determined using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. SIRT1 gene polymorphisms were determined by PCR-confronting two-pair primers methods. RESULTS: The FOXO3A rs4946936 and SIRT1 rs7069102 gene polymorphisms were positively correlated with EOP and disease severity. The GG genotype frequency of SIRT1 rs7069102 gene polymorphisms was increased in severe EOP. The CC frequency of FOXO3A rs4946936 was increased in EOP with nail disorders. CONCLUSION: The rs7069102 gene polymorphism of SIRT1 and rs4946936 polymorphism of FOXO3A are associated with early onset psoriasis; this may be responsible for increased keratinocyte proliferation in the pathogenesis of psoriasis and disease severity.

Iatrogenic Cushing's Syndrome with Subsequent Adrenal Insufficiency in a Patient with Psoriasis Vulgaris Using Topical Steroids.

Iatrogenic Cushing's syndrome (ICS) is usually related to prolonged and/or high-dose oral or parenteral steroid use. Psoriasis vulgaris (PV) is chronic inflammatory disease and characterized by periods of attack and remission. Topical steroid (TS) is the first choice of treatment for localized and mild PV. The development of systemic side effects of the steroids is usually not observed after TS application. But the risk of developing ICS still exists. In the literature, there are a few adult cases who developed ICS and subsequent adrenal insufficiency associated with TS. In this article, a male patient with PV developing ICS and secondary adrenal insufficiency after treatment of TS for 12 years is presented.

Risk Factors for Premature Hair Graying in Young Turkish Adults.

BACKGROUND: Premature hair graying (PHG) is a common condition resulting in loss of self-esteem. Studies investigating PHG risk factors for both sexes with a large number of patients are scarce. We sought to investigate the socioclinical risk factors for PHG in young Turkish men and women and the differences between the sexes. METHODS: A cross-sectional study was conducted in 1,119 participants who answered a survey about PHG and some socioclinical characteristics between February and July 2015. The number of gray hairs, onset age of hair graying, and family history of PHG were asked about, as well as demographic characteristics, anthropometric measures, body mass index, smoking, alcohol consumption, sports life, diet, medical history, educational status, occupation, marital status, monthly income, and Fitzpatrick skin type. RESULTS: Of 1,119 participants, 315 (28.1%) had PHG and 804 did not. Maternal and paternal PHG, alcohol consumption, presence of chronic disease, educational status, hair loss, perceived stress scale (PSS) score, age, and height were significantly higher in subjects with PHG. Rates of maternal and paternal PHG were high in women with PHG, and the rate of paternal PHG was high in men with PHG. According to the multivariate ordinal regression analysis, PSS score, age, hair loss, and family history of PHG were correlated with the severity of PHG. CONCLUSION: PHG is closely related to factors causing oxidative stress, such as emotional stress, alcohol consumption, and chronic diseases in genetically predisposed men and women.

The relationship between rosacea and insulin resistance and metabolic syndrome.

Rosacea is a chronic inflammatory skin disease affecting the face. A positive correlation has been found between rosacea and cardiovascular diseases. We sought to investigate the relation between rosacea and metabolic syndrome (MS) and insulin resistance (IR). Between January and June 2015, a case-control study including 47 age-, gender-, and body mass index (BMI)-matched rosacea patients and 50 controls was conducted. Demographic data, clinical features of rosacea patients, anthropometric measures, laboratory findings, blood pressure levels, BMI, smoking history, alcohol consumption, sports life, family history of cardiovascular disease, and presence of MS and IR were recorded. Forty-seven rosacea patients (12 men and 35 women; age range: 35-68 years) and 50 controls (11 men and 39 women; age range: 38-78 years) were included in our study. Of 47 rosacea patients, 24 had erythematotelangiectatic type, 22 had papulopustular type, and one had phymatous type. Whereas the rate of IR was significantly higher in the rosacea group, there was no significant difference in the rate of MS between rosacea and the control group (p = 0.009 and p = 0.186, respectively). In addition, the rosacea group had significantly higher fasting blood glucose, total cholesterol, and systolic and diastolic blood pressure levels (p<0.05). Mean levels of LDL, triglyceride, total cholesterol and CRP were significantly higher than in the control group (p<0.05). Our findings suggest that there is a relationship between rosacea and IR and some parameters of cardiovascular risk factors. We recommend investigation of IR in rosacea patients.

A first case report of diffuse acneiform eruption caused by capecitabine in a patient with small-cell neuroendocrine lung carcinoma.

Capecitabine is a chemotherapeutic agent which is converted to fluorouracil by thymidine phosphorylase in human body. It is one of the commonly used agents in colorectal and metastatic breast cancers. Hand-foot syndrome is most commonly observed adverse effect of capecitabine; however, it has several adverse cutaneous and mucosal effects. To the best of our knowledge, no case with acneiform eruption has been reported so far. Here, we presented a 54-year-old man with development of capecitabine-related acneiform drug eruption.

Pustular eruption induced by etanercept in a patient with ankylosing spondylitis: a rare side effect.

Etanercept is a tumor necrosis factor alpha (TNF-a) antagonist with anti-inflammatory effects. It is used in the treatment of dermatologic and rheumatologic diseases such as rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. However, etanercept has various cutaneous and systemic side effects. Herein, we report a case of generalized pustular eruption due to etanercept therapy in an ankylosing spondylitis patient and review pustular diseases.

Pregnancy as a possible etiologic factor in erythema annulare centrifugum.

Immunologic, endocrine, metabolic, and vascular changes that occur during pregnancy may adversely affect the skin. This article describes a patient who developed erythema annulare centrifugum during pregnancy. The eruptions disappeared shortly before delivery. To the author's knowledge, this is only the third report of erythema annulare centrifugum associated with pregnancy. This article discusses the possible connections between erythema annulare centrifugum and pregnancy that may be demonstrated in this case.

Melanocytic nevi in 2783 children and adolescents in Turkey.

This study investigated the numbers of melanocytic nevi in Turkish children and adolescents. The research was conducted on 2783 subjects (age range, 7-14 yrs) at three elementary schools in Malatya, Turkey (latitude 38 degrees N). Numbers of melanocytic nevi per subject were counted using a standard international protocol. Comparisons were made with subjects categorized according to age, sex and skin type. The mean melanocytic nevus count was 1.07 +/- 2.37. A significant positive correlation was found between nevus count and age (p < 0.001). The mean count for boys was significantly higher than that for girls (p < 0.001). Subjects with skin type II had a higher mean melanocytic nevus count than the other three groups. This is the first study related to numbers of melanocytic nevi in Turkey. The findings reveal that Turkish children and adolescents have few melanocytic nevi compared to those elsewhere in the world. In line with previous reports on other populations, analysis showed that older age, skin type II, and male sex are associated with higher melanocytic nevus counts. The results underline the importance of ethnic background in melanocytic nevus development.

Pruritic eruption with reticular pigmentation: confluent and reticulate papillomatosis.

A 28-year-old man presented with a 2-year history of a pruritic eruption on his neck, chest, back, axillae, and antecubital and pubic areas. The patient had been previously treated with topical and systemic antifungal therapy for a long time, but showed no response. Examination revealed the typical clinical and histological features of confluent and reticulate papillomatosis. The patient responded well to oral doxycycline.

Basal cell carcinoma in outdoor versus indoor workers in Turkey.

BACKGROUND: Basal cell carcinoma remains a significant health problem, and is most common in people of Caucasian origin with significant sun exposure. This study investigated differences between two groups of Turkish patients with basal cell carcinoma: indoor workers versus outdoor workers. METHODS: One hundred and twenty-one patients with primary basal cell carcinoma were categorized as outdoor (Group OW) or indoor workers (Group IW), according to sun exposure at work. Findings for age, sex, skin type, tumor location, and histologic subtype/aggression were compared. RESULTS: The mean age of Group IW was lower than that of Group OW (57.3 +/- 9.2 vs. 65.8 +/- 12.2 years, respectively). Group OW comprised more men than women (63.4% vs. 36.6%, respectively), whereas women predominated in Group IW (62% vs. 38%, respectively). The facial cheek was a more frequent tumor site in Group IW than in Group OW (20% vs. 7.0%, respectively). There were no statistical differences with respect to skin types or histological subtypes; however, Group OW had a higher proportion of aggressive subtypes than Group IW (25.4% vs. 10%, respectively). CONCLUSIONS: The results in the Turkish population of the study suggest that basal cell carcinoma may develop in indoor workers (intermittent sun exposure) earlier than in outdoor workers with chronic sun-exposure, but more aggressive subtypes are more likely to be linked with chronic sun-exposure.

Scalp ulcer as first sign of cholangiocarcinoma.

Metastases from distant primary tumors are rarely the first indicators of cancer. However, cutaneous metastases are not uncommon in cases of internal malignancy. This article describes the case of a 65-year-old man with cutaneous metastasis of cholangiocarcinoma who presented with a scalp ulcer as the only initial sign. This is only the third reported case of cholangiocarcinoma with distant cutaneous metastasis.

A comparative study of superoxide dismutase, catalase, and glutathione peroxidase activities and nitrate levels in vitiligo patients.

BACKGROUND: Several groups have shown the involvement of oxidative stress in the pathophysiology of vitiligo. METHODS: In this study, we examined the erythrocyte and plasma activities of glutathione peroxidase and Cu/Zn superoxide dismutase, plasma nitrite/nitrate levels, and erythrocyte catalase activity in 23 vitiligo patients and 25 controls. RESULTS: The results show that erythrocyte superoxide dismutase activity and plasma nitrite/nitrate levels are high in vitiligo patients. CONCLUSIONS: Our study confirms that oxidative stress is involved in the pathophysiology of vitiligo, as indicated by the high levels of erythrocyte superoxide dismutase activity and plasma nitrite/nitrate.