Sea Buckthorn (Hippophaë rhamnoides L.) Oil Improves Atopic Dermatitis-Like Skin Lesions via Inhibition of NF-κB and STAT1 Activation.

BACKGROUND AND OBJECTIVES: The objective of this study was to evaluate the topical effects of sea buckthorn (SBT) oil on atopic dermatitis (AD)-like lesions in a mouse model generated by repeated topical administration of DNCB in BALB/c mice. METHODS: DNCB was applied repeatedly on the dorsal skin of mice to induce AD-like lesions. Following AD induction, SBT oil was applied daily on the dorsal skin for 4 weeks. The severity of skin lesions was examined macroscopically and histologically. We further measured the production of MDC/CCL22 and TARC/CCL17 in IFN-γ/TNF-α activated HaCaT cells. RESULTS: Topically applied SBT oil in DNCB-treated mice ameliorated the severity score of dermatitis, decreased epidermal thickness, reduced spleen and lymph node weights, and prevented mast cell infiltration. In addition, SBT oil suppressed the Th2 chemokines TARC and MDC via dose-dependent inhibition of NF-κB, JAK2/STAT1, and p38-MAPK signaling pathways in IFN-γ/TNF-α-activated HaCaT cells. CONCLUSION: These results suggest that SBT oil had a beneficial effect on AD-like skin lesions, partially via inhibition of the Th2 chemokines TARC and MDC in inflamed skin.

T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes.

BACKGROUND: Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing. METHODS: HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry. RESULTS: IL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions. CONCLUSIONS: Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.

R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma.

OBJECTIVES: Mutations in the GJB2 gene encoding connexin 26 (Cx26) are major causes of hereditary deafness. This study aimed to characterize the mutation profiles of the GJB2 gene in a Chinese family with sensorineural hearing loss. METHODS: A Chinese family that included three individuals with sensorineural hearing loss and palmoplantar keratoderma underwent complete physical examinations, audiological examinations including pure tone audiometry and auditory brainstem response, skin pathological examination, and temporal CT scans. The entire coding region of GJB2, GJB3, GJB6, and the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN) were sequenced. Structural analysis was performed to detect the effects of mutation on the tertiary structure of Cx26. RESULTS: A dominant GJB2 mutation, c.224G>A (p.Arg75Gln, p.R75Q), was detected in the family. No other mutation was identified in GJB2, GJB3, GJB6, or the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN). Structural analysis revealed that the p.R75Q mutation likely affects the structural stability and permeation properties of the Cx26 gap junction channel. CONCLUSION: Our findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma.

Clearance of genital warts in pregnant women by mild local hyperthermia: a pilot report.

Genital warts acquired during pregnancy tend to grow fast, and management is challenging. We treated two cases of primipara with extensive genital warts by local hyperthermia at 44°C for 30 minutes a day for 3 consecutive days plus 2 additional days 1 week later, then once a week till there showed signs of clinical regression. The warty lesions in the patients resolved in 5 and 7 weeks, respectively. There was no sign of recurrence during a 6-month follow-up. This suggests that local hyperthermia seems to be a promising method for treating genital warts in pregnant women.

Erratum to "changes in cutaneous sensory nerve fibers induced by skin-scratching in mice".

BACKGROUND: Skin-scratching behavior, a common response observed in patients with pruritus, is supposed to promote the sprouting of cutaneous sensory nerve fibers. Thus, it sometimes exacerbates the original lesions. However, the precise changes that develop in cutaneous sensory nerve fibers after skin-scratching have not yet been elucidated. OBJECTIVE: To investigate how and what kinds of cutaneous sensory nerve fibers increase and how nerve growth factor (NGF) and its receptors change after skin-scratching. METHODS: After scratching the dorsal skin of anesthetized ICR mice, change in cutaneous nerve fibers was detected by immunofluorescence for protein gene product 9.5 (PGP9.5), substance P (SP) and/or calcitonin gene-related peptide (CGRP). To investigate the involvement of NGF signaling, the production of NGF and the expression of its receptors were examined using ELISA and/or immunofluorescence, respectively. RESULTS: Skin-scratching dramatically induced the sprouting of cutaneous nerve fibers. Both dermal and epidermal nerve fibers began to increase and reached a peak at days 3-7. At the same time, nerve fibers containing SP or CGRP increased significantly. NGF in the scratched skin increased immediately and reached a peak at days 1-3. The expression of NGF receptors, such as phosphorylated trk A and p75, on nerve fibers was remarkably upregulated within 2 days. CONCLUSIONS: Skin-scratching induced the sprouting of cutaneous sensory nerve fibers in the skin within several days, thus possibly leading to enhanced neurogenic inflammation. Analysis of the expression of NGF and its receptors suggest that NGF signaling may be, at least in part, involved in these changes.

Changes in cutaneous sensory nerve fibers induced by skin-scratching in mice.

BACKGROUND: Skin-scratching behavior, a common response observed in patients with pruritus, is supposed to promote the sprouting of cutaneous sensory nerve fibers. Thus, it sometimes exacerbates the original lesions. However, the precise changes that develop in cutaneous sensory nerve fibers after skin-scratching have not yet been elucidated. OBJECTIVE: To investigate how and what kinds of cutaneous sensory nerve fibers increase and how nerve growth factor (NGF) and its receptors change after skin-scratching. METHODS: After scratching the dorsal skin of anesthetized ICR mice, change in cutaneous nerve fibers was detected by immunofluorescence for protein gene product 9.5 (PGP9.5), substance P (SP) and/or calcitonin gene-related peptide (CGRP). To investigate the involvement of NGF signaling, the production of NGF and the expression of its receptors were examined using ELISA and/or immunofluorescence, respectively. RESULTS: Skin-scratching dramatically induced the sprouting of cutaneous nerve fibers. Both dermal and epidermal nerve fibers began to increase and reached a peak at days 3-7. At the same time, nerve fibers containing SP or CGRP increased significantly. NGF in the scratched skin increased immediately and reached a peak at days 1-3. The expression of NGF receptors, such as phosphorylated trk A and p75, on nerve fibers was remarkably upregulated within 2 days. CONCLUSIONS: Skin-scratching induced the sprouting of cutaneous sensory nerve fibers in the skin within several days, thus possibly leading to enhanced neurogenic inflammation. Analyses of the expression of NGF and its receptors suggest that NGF signaling may be, at least in part, involved in these changes.