Chih-Chieh Chan

Human leucocyte antigen-Cw6 as a predictor for clinical response to ustekinumab, an interleukin-12/23 blocker, in Chinese patients with psoriasis: a retrospective analysis.

Ustekinumab, an interleukin‐12/23 inhibitor, is effective in the treatment of psoriasis. A recent Italian study showed more favourable response to ustekinumab in patients with positive human leucocyte antigen (HLA)‐Cw6. Nonetheless, there are differences in genetic susceptibility to psoriasis between races, and no studies have specifically assessed the candidate genetic markers in predicting therapy outcome in Chinese patients with psoriasis treated with ustekinumab.

High-throughput reconstitution of epithelial–mesenchymal interaction in folliculoid microtissues by biomaterial-facilitated self-assembly of dissociated heterotypic adult cells

The aim of this study was to develop a method for efficient production of folliculoid keratinocyte-dermal papilla (DP) microtissues to facilitate epithelial-mesenchymal interaction. The behavior of DP cells and adult keratinocytes from hairless skin on poly(ethylene-co-vinyl alcohol) (EVAL) surface was investigated. Keratinocytes, poorly adherent both to substrate and between homotypic cells, become suspended disperse cells after homotypic cell seeding. Seeded simultaneously, keratinocytes and DP cells are able to aggregate into spheroidal microtissues. Dynamical analysis shows that DP cells act as a carrier in the process due to the heterotypic intercellular adhesion. DP cells attach faster to EVAL and start to aggregate. Keratinocytes adhere to DP cells and are then carried by DP cells to form initial hybrid aggregates. Due to the high motility of DP cells, these hybrid aggregates move collectively as clusters and merge into larger spheroids which subsequently detach from the substratum and can be easily collected. Compared with random cell distribution in spheroids generated in hanging drops, these hybrid spheroids have a preferential compartmented core-shell structure: an aggregated DP cell core surrounded by a keratinocyte shell. In addition to ameliorated DP signature gene expression, keratinocytes show down-regulated epidermal terminal differentiation and enhanced follicular differentiation. Functionally, these microtissues are able to grow hairs in vivo. This work sheds light on the complex effects and dynamics of cell-cell and cell-substratum interaction in the patterning of heterotypic cells into tissue forms and is of potential to be applied to mass generation of other epithelial organ primordia in vitro.

Scalable production of controllable dermal papilla spheroids on PVA surfaces and the effects of spheroid size on hair follicle regeneration

Organ size and numbers are vital issues in bioengineering for hair follicle (HF) regeneration. Murine HF dermal papilla (DP) cells are able to induce HF neogenesis when transplanted as aggregates. However, how the preparation of murine and human DP aggregates affects HF inductivity and the size of regenerated HF is yet to be determined. Here we report a scalable method for production of controllable human and rat DP spheroids in general labs for reproducible experiments. Compared with more hydrophobic polyethylene and poly(ethylene-co-vinyl alcohol), DP cells are poorly adhesive to hydrophilic polyvinyl alcohol (PVA). Seeded in PVA-coated 96-welled commercial PCR tube arrays, DP cells quickly aggregate into single spheroids with progressive compaction. Varying seeded cell numbers and culture periods enables us to control the size and cell number of the spheroids. The spheroids obtained have high viability and preserve DP characters. A proof of principle experiment was conducted to examine the size effect on the efficiency and efficacy of HF regeneration. We found that both human and rat DP spheroids are able to induce HF neogenesis and larger DP spheroids exhibit higher HF inductivity. However, the average diameter of regenerated hair fiber did not significantly change with the increasing size of transplanted DP spheroids. The result suggests that an appropriate size of DP spheroid is essential for HF inductivity, but its size cannot be directly translated to a thicker regenerated hair. Our results also have implications on the efficiency and efficacy in the regeneration of other epithelial organs.

The clinical anti-aging effects of topical kinetin and niacinamide in Asians: a randomized, double-blind, placebo-controlled, split-face comparative trial

Background  Kinetin and niacinamide are used in the cosmetic industry as anti‐aging agents. Neither the interactive/additive effects of these compounds nor the anti‐aging efficacy on Asian skin has been studied.

The enhancement of dermal papilla cell aggregation by extracellular matrix proteins through effects on cell-substratum adhesivity and cell motility.

Generally, cells tend to aggregate on a substratum with lower cell adhesivity. However, it also leads to compromised cell growth and higher cell loss after seeding. This study is aimed at tackling this dilemma by extracellular matrix (ECM) protein coating of a lower adhesive substratum poly(ethylene-co-vinyl alcohol) (EVAL) that has been shown to facilitate hair follicle dermal papilla (DP) spheroid formation. We found that coating with either fibronectin (Fn), collagen I, or collagen IV yields higher adhesivity and cell growth than that with laminin. However, cells can only aggregate on uncoated or Fn-coated EVAL. Quantitatively, Fn coating increases the number of spheroids by 67%. Analysis of cell migration reveals that collagen I, collagen IV and laminin coatings reduce cell motility, while Fn coating keeps cells highly motile. Inhibition of cell migration hinders spheroid formation. In addition, disruption of Fn function does not significantly compromise intercellular adhesion. Hence, Fn enhances cell aggregation by enhancing cell attachment, cell growth and cell motility. Our study demonstrates that intercellular organization as spheroids or flat monolayers is switchable by specific ECM protein coating and preserving cell motility is vital to cell aggregation. In addition to generation of spheroidal DP microtissues for hair follicle regeneration and large-scale production of aggregates of other cells, this strategy can help to regulate the tissue-substrate adhesivity and tissue spreadability on the surface of implantable materials.

The Effects of Depilatory Agents as Penetration Enhancers on Human Stratum Corneum Structures

The depilatory cream thioglycolate has been shown to be an effective enhancer for transdermal drug delivery. However the mechanism remains unknown. In addition, it may also increase the risk of permeation of exogenous toxic agents across skin in depilatory cream users. The aim of this study was to characterize its effect on the transepidermal route and the associated structural alterations. Fresh human skin was treated with a depilatory cream for 10 minutes and then permeated with fluorescent model drugs. The penetration of model drugs was then imaged and quantified. The structural alternations of stratum corneum were assessed by multi-photon imaging, histology, Nile red staining, and electron microscopy. Our results show that penetration of both hydrophilic and hydrophobic model drugs across stratum corneum was enhanced. Disruption of cellular integrity and focal detachment of superficial corneocytes was observed in multi-photon imaging. In addition, nile red staining showed disorganized lipid distribution. Finally, ultrastructural analysis revealed disruption of intracellular keratin matrix, protein cell envelope, and regular lamellar intercellular lipid packing. Because intracellular and intercellular structures were altered, our results suggest that depilatory agents enhance transepidermal drug delivery by reducing resistance in both transcellular and intercellular routes of stratum corneum.

Risk Factor Analysis for the Immunogenicity of Adalimumab Associated with Decreased Clinical Response in Chinese Patients with Psoriasis

Although anti-drug antibodies against biologics have been associated with decreased clinical efficacy, the immunogenicity of biologics seems to vary between drugs, diseases and ethnicities. This study aims to investigate the predictors for the formation of anti-adalimumab antibodies (AAA) and the clinical consequences of AAA formation. In 53 Chinese psoriatic patients treated with adalimumab, AAA was detected in 50.9%. Differences in Psoriasis Area and Severity Index 75 (PASI75) response rates among patients with and without AAA were significant (44.4% vs. 88.5%; p = 0.001). Patients with AAA had significantly lower trough concentrations of adalimumab than those without AAA. Risk factor analysis showed that treatment interruption, low trough adalimumab concentration, absence of concomitant methotrexate use and biologics switching were associated with a higher AAA titre. The treatment pattern of biologics influences the risk of AAA formation, thereby leading to reduced efficacy of adalimumab.

Visible red light enhances physiological anagen entry in vivo and has direct and indirect stimulative effects in vitro.

Hair follicles are located at the interface of the external and internal environments and their cycling has been shown to be regulated by intra‐ and extra‐follicular factors. The aim of this study is to examine whether or how hair follicles respond to visible light.

Human papillomavirus type 5 infection in a patient with Hailey–Hailey disease successfully treated with imiquimod

of the skin lesions showed in two cases the ascent of adipocytes into the upper dermis, commonly described in post-traumatic piezogenic papules of the feet. Therefore, we postulate that postnatally acquired stricture could share the same traumatic mechanism as the compression described in the ’extrinsic’ model for pathogenesis of amniotic band syndrome and may represent a new aetiology of raised limb bands.

Porphyria Cutanea Tarda

n engl j med 365;12 nejm.org september 22, 2011 1128 A 51-year-old man with a history of heavy alcohol use, chronic hepatitis C virus (HCV) infection, and hepatic cirrhosis presented to his physician with an 8-month history of periorbital hair growth. On examination, healing crusts and scars were evident in sun-exposed areas. He described skin photosensitivity and intermittent painful blistering over the nape of the neck, the forearms, and the backs of the hands (Panel A). The patient’s urine had pink fluorescence under a Wood’s lamp, suggesting the presence of uroporphyrin (Panel B, a urine sample from the patient [indicated by an asterisk] and one from a normal control subject [N] under white light; Panel C, the same two urine samples under ultraviolet A light). A diagnosis of porphyria cutanea tarda was confirmed when marked uroporphyrinuria was shown on laboratory analysis. Porphyria cutanea tarda results from decreased activity of the uroporphyrinogen decarboxylase enzyme. Although the mechanism is unknown, the sporadic form of the disease is strongly associated with chronic HCV infection. Facial hypertrichosis is common and may serve as a diagnostic clue. Although treatment of the patient’s chronic HCV infection was considered inadvisable by his hepatologist, low-dose oral hydroxychloroquine, skin photoprotection, and alcohol cessation successfully controlled the cutaneous eruptions within 6 months.