Yiguo Feng

Wnt/β-Catenin and Wnt5a/Ca Pathways Regulate Proliferation and Apoptosis of Keratinocytes in Psoriasis Lesions.

Background/Aims: Wnt5a is overexpressed in psoriasis lesions, however the mechanism by which Wnt5a is involved in the pathogenesis of psoriasis is not clear. To address this, the expression of Wnt5a in psoriatic lesions and its effect on keratinocyte cell proliferation and apoptosis was examined in vitro. Methods: The expression levels of WNT5A, and genes encoding its receptors frizzled2 (FZD2) and frizzled5 (FZD5) were examined in samples obtained from individuals with psoriasis and healthy controls. Knockdown of Wnt5a with short interfering (si)RNAs was performed in cultured HaCaT keratinocytes and normal human keratinocytes (NHK), and the expression of Wnt5a, protein kinase C (PKC), and β-catenin were determined, and cell cycle activity, proliferation and apoptosis were assessed. Results: The expression of WNT5A, FZD2 and FZD5 mRNA and protein were increased in psoriatic lesions. Wnt5a knockdown suppressed proliferation and induced apoptosis in HaCaT and NHK cells. Additionally, expression of PCNA, MKI67, CCND1, BCL2, CTNNB1, and genes encoding PKC and survivin were downregulated, whereas CASP3 was upregulated. The mRNA levels of the Wnt pathway inhibitors DKK1 and SFRP1 were upregulated, Western blotting analyses demonstrated reduction in β-catenin and PKC protein levels. Conclusion: Knockdown of Wnt5a suppresses the proliferation of keratinocytes and induces apoptosis by inhibiting the Wnt/β-catenin or Wnt5a/Ca2+ pathways.

Predictive factors for adverse dermatological events during pegylated/interferon alpha and ribavirin treatment for hepatitis C

BACKGROUND Treatment of chronic hepatitis C (CHC) with pegylated interferon-alpha/ribavirin is associated with well-characterized dermatological adverse events (AEs), which can lead to premature discontinuation of treatment. OBJECTIVE To investigate the incidence and spectrum of dermatological AEs during CHC treatment with interferon-alpha plus ribavirin and analyzed factors predisposing patients to such reactions. STUDY DESIGN Between January 2008 and December 2012, 152 CHC patients who had received interferon/pegylated interferon plus ribavirin therapy were enrolled in this retrospective study. To determine which factors were associated with dermatological AE development, a Cox proportional-hazards regression analysis was performed. RESULTS Thirty dermatological AEs were recorded in 28 (18.4%) patients. These reactions included 14 (9.2%) patients with eczematous reactions, four (2.6%) patients with xerosis, three (2.0%) patients with new-onset or exacerbation of psoriasis, two (1.3%) patients with lichenoid eruption, two (1.3%) patients with diffuse folliculitis and one patient with lichen planus, alopecia areata, hypermelanosis, and necrosis of the skin and toenails. Application of the Cox proportional-hazards model revealed that age older than 60 years (HR=1.070; 95% CI: 1.043-1.096), pre-existing anaphylaxis/skin disease (HR=2.612; 95% CI: 1.593-3.324), cirrhosis (HR=1.863; 95% CI: 1.047-3.013), and treatment with pegylated interferon formulations (HR=1.930; 95% CI: 1.052-3.687) were associated with occurrence of dermatologic AEs. Twenty-seven (90%) skin conditions were classified as mild to moderate, while one case (3.3%) warranted premature discontinuation of treatment. CONCLUSION Dermatological AEs resulting from interferon-alpha/ribavirin treatment of CHC contribute to a wide spectrum involve the skin, mucous membrane, hair, and nails. These dermatological AEs correlated with older age, previous skin condition, cirrhosis, and use of pegylated interferon formulations.

A novel splicing mutation and haplotype analysis of the FECH gene in a Chinese family with erythropoietic protoporphyria

Background  Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of haeme biosynthesis resulting from a partial decrease in ferrochelatase (FECH) activity leading to excessive accumulation of protoporphyrin. Clinical manifestation normally requires coinheritance of a common hypomorphic FECH allele and a deleterious FECH mutation.

Vitiligo nonsurgical treatment: a review of latest treatment researches

Vitiligo is a common depigmenting acquired disorder affecting about 1–2% of the world population, regardless of race, ethnic background, or gender. It is characterized by the appearance of milky white maculae because of a loss of melanocytes. The disfiguring nature of vitiligo causes high psychosocial morbidity. This is especially pronounced in populations with darker skin tone, likely because of the marked contrast. A variety of nonsurgical treatment regimens are currently employed in vitiligo. We reviewed the latest studies carried out on different nonsurgical treatment modalities used in vitiligo. All nonsurgical treatment aid to repigment or depigmentation the skin, however, many of them require a prolonged treatment course and may yield minimal results as well as carry unwanted side effects. There is a need for further research into the causes of vitiligo and into discovering better treatments.

Wnt5a is involved in the pathogenesis of cutaneous lichen planus.

Cutaneous lichen planus (CLP) is a chronic inflammatory and immune‐mediated disease. Wnt5a is one of the most extensively studied Wnt proteins, and has important functions in stimulating inflammation, cell proliferation, cell fate determination and cell differentiation. Wnt5a expression in CLP has not been comprehensively studied to date.

Delayed-onset pachyonychia congenita caused by a novel mutation in the V2 domain of keratin 6b

explanation for the discrepancy relates to the degree of effect on various tissues to the target-specificity of imatinib because different tissues may have diverse c-kit isotypes. Our patient showed graying of more than 50% of the scalp and pubic hair with generalized skin hypopigmentation, but the rest of the hairs were not involved. This may suggest that imatinib has target-specificity or a varying degree of ckit inhibition not only between skin and hair but also between each hair. Besides hair graying, our patient also showed diffuse hair loss of the scalp, which is also a possible side-effect of imatinib. It is associated with plateletderived growth factor receptor (PDGFR)-regulated maintenance of the anagen phase of the hair cycle. The hair loss is thought to be related to inhibition of PDGFR by imatinib with resulting telonization of the hair follicles that eventually led to telogen effluvium. Both hair graying and hair loss are stressful for young female patients on antitumor therapy. Therefore, physicians should be aware of hair graying as an additional possible sideeffect of imatinib and notify patients.

Congenital monilethrix and hereditary unilateral external auditory canal atresia are co‐inherited in a Chinese pedigree with recurrent KRT86 mutation

form caries. Radiological examinations showed bone resorption with ungual tuberosity of the distal phalanx on the second, third, fourth and fifth right fingers and on the left little finger (Fig. 3); subluxations of the third, fourth and fifth metatarsophalangeal joints on the right foot; bone resorption and tapering of distal phalanx on both feet. No abnormalities of his hands and feet were mentioned after radiographs taken 3 years prior. Calcaneal bone density was decreased with bone density test. Dermatoscopic examination of his scalp hair showed scanty, irregularly anfractuous and short hair of less than 1 cm (Fig. 4). Histopathological examination showed a verruciform hyperplasia lesion of high grade hyperkeratosis accompanied by parakeratosis, in addition to irregular hyperplasia of the epidermis, presence of physaliferous cells and large keratohyaline granules of the upper epidermis. Only the papillary region was seen in the dermis with vascular proliferation, dilation and congestion. The patient had been treated with viaminate (25 mg daily) since the age of 3.5 years, but gained no obvious improvement in itching, pain and hyperkeratosis. After taking acitretin (10 mg daily) since the age of 5 years, he showed partial improvement in mentioned symptoms and signs, while hyperkeratosis became worse with reduced acitretin dose or discontinued application with a maximum 3 days’ withdrawal time. He had been on the same dose of acitretin since then. Unlike joint laxity reported previously, the ankylosis (knee and ankle joints) observed in this patient could be related to long-term pain and severe keratoderma that impeded his mobility. Treatment of this disorder is still problematic. This patient gained a partial improvement in itching, pain and hyperkeratosis from treatment with acitretin. However, he developed bone changes and growth retardation that could be related to acitretin after 3 years’ therapy. In our opinion, oral acitretin might be an effective therapy in amelioration of symptoms and signs of Olmsted syndrome while adverse effects might also need to be considered. Acitretin seems unfit for the treatment of Olmsted syndrome in children and adolescents.

Atrichia with Papular Lesions in a Chinese Family Caused by Novel Compound Heterozygous Mutations and Literature Review

Background: Congenital atrichia with papular lesions (APL) is characterized by complete absence of body hair shortly after birth, along with papules, and caused by mutations in the hairless gene (HR). Objective: To investigate whether APL with HR mutations might also be found among patients in non-consanguineous Chinese families and to discuss the phenotypic variations with the same mutations. Methods: DNA sequencing of the HR was performed in the Chinese pedigree and in 100 controls. Results: A nonsense mutation c.T2265A in the patient and his father as well as a 2bp deletion (3482delCT) in the patient and his mother were detected. Conclusion: Our study identified the first mutation in exon 10 in HR as well as the second novel compound heterozygous mutations in a Chinese family, also adding new variants to the knowledge of HR mutations in APL. Phenotypic heterogeneity in congenital atrichia might be subject to the founder genes or modifier genes.