Precise role of dermal fibroblasts on melanocyte pigmentation

Publication date: Available online 1 July 2017
Source:Journal of Dermatological Science
Author(s): Yinjuan Wang, Céline Viennet, Sophie Robin, Jean-Yves Berthon, Li He, Philippe Humbert
Dermal fibroblasts are traditionally recognized as synthesizing, remodeling and depositing collagen and extracellular matrix, the structural framework for tissues, helping to bring thickness and firmness to the skin. However, the role of fibroblasts on skin pigmentation arouses concern recently. More is known about the interactions between epidermal melanocytes and keratinocytes.This review highlights the importance of fibroblast-derived melanogenic paracrine mediators in the regulation of melanocyte activities. Fibroblasts act on melanocytes directly and indirectly through neighboring cells by secreting a large number of cytokines (SCF), proteins (DKK1, sFRP, Sema7a, CCN, FAP-α) and growth factors (KGF, HGF, bFGF, NT-3, NRG-1, TGF-β) which bind to receptors and modulate intracellular signaling cascades (MAPK/ERK, cAMP/PKA, Wnt/β-catenin, PI3K/Akt) related to melanocyte functions. These factors influence the growth, the pigmentation of melanocytes via the expression of melanin-producing enzymes and melanosome transfer, as well as their dendricity, mobility and adhesive properties. Thus, fibroblasts are implicated in both skin physiological and pathological pigmentation. In order to investigate their contribution, various in vitro models have been developed, based on cellular senescence. UV exposure, a major factor implicated in pigmentary disorders, may affect the secretory crosstalk between dermal and epithelial cells.Therefore, identification of the interactions between fibroblasts and melanocytes could provide novel insights not only for the development of melanogenic agents in the clinical and cosmetic fields, but also for a better understanding of the melanocyte biology and melanogenesis regulation.



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CCL3/MIP1α represents a biomarker but not a mandatory cytokine for disease development in experimental epidermolysis bullosa acquisita

Publication date: Available online 30 June 2017
Source:Journal of Dermatological Science
Author(s): Michael Kasperkiewicz, Kathrin Kalies, Rene Pagel, Katja Bieber, Detlef Zillikens, Ralf J. Ludwig




http://ift.tt/2ssNpwj

Polysaccharide matrices used in 3D in vitro cell culture systems

Publication date: October 2017
Source:Biomaterials, Volume 141
Author(s): Dorina Diekjürgen, David W. Grainger
Polysaccharides comprise a diverse class of polymeric materials with a history of proven biocompatibility and continual use as biomaterials. Recent focus on new matrices appropriate for three-dimensional (3D) cell culture offers new opportunities to apply polysaccharides as extracellular matrix mimics. However, chemical and structural bases for specific cell-polysaccharide interactions essential for their utility as 3-D cell matrices are not well defined. This review describes how these naturally sourced biomaterials satisfy several key properties for current 3D cell culture needs and can also be synthetically modified or blended with additional components to tailor their cell engagement properties. Beyond their benign interactions with many cell types in cultures, their economical and high quality sourcing, optical clarity for ex situ analytical interrogation and in situ gelation represent important properties of these polymers for 3D cell culture applications. Continued diversification of their versatile glycan chemistry, new bio-synthetic sourcing strategies and elucidation of new cell-specific properties are attractive to expand the polysaccharide polymer utility for cell culture needs. Many 3D cell culture priorities are addressed with the portfolio of polysaccharide materials available and under development. This review provides a critical analysis of their properties, capabilities and challenges in 3D cell culture applications.



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L’infection à Zika virus : mise au point

Publication date: Available online 30 June 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Guillier, E. Amazan, A. Aoun, E. Baubion, C. Derancourt
Le virus Zika (ZIKV), initialement identifié en 1947, est un Flavivirus ré-émergent, principalement transmis par les piqûres de moustiques du genre Aedes. Jusqu'aux récentes épidémies dans les îles du Pacifique et en Amérique centrale et du sud, il était réputé à l'origine d'une maladie bénigne, asymptomatique dans la majorité des cas, ou avec des symptômes modérés non spécifiques (fièvre, éruption, conjonctivite, arthralgies…). Au cours de l'épidémie actuelle, d'une ampleur inédite, de nouveaux modes de transmission (transfusionnel, périnatal, sexuel) et des complications neurologiques sévères telles que des malformations congénitales chez les fœtus de mères infectées et des syndromes de Guillain-Barré chez l'adulte ont été mis en évidence. Cette situation, dans un contexte de potentielle pandémie mondiale à venir, a amené l'Organisation mondiale de la santé (OMS) à déclarer l'infection à ZIKV urgence de santé publique de portée internationale en février 2016.Zika Virus (ZIKV), originally identified in 1947, is a re-emerging Flavivirus transmitted mainly through bites by Aedes mosquitos. Until the recent outbreaks in the Pacific islands and Central and South America, it was known to cause benign disease, in most cases asymptomatic or with mild and nonspecific symptoms (fever, rash, conjunctivitis, arthralgia, etc.). The unprecedented current epidemic has highlighted new modes of transmission (through blood, perinatally and sexually) as well as serious neurological complications such as congenital defects in the fetuses of infected mothers and Guillain-Barre syndrome in adults. This situation, coupled with the threat of worldwide spread, prompted the WHO to declare the ZIKV a public health emergency of international concern in February 2016.



http://ift.tt/2tbP46I

L’infection à Zika virus : mise au point

Publication date: Available online 30 June 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Guillier, E. Amazan, A. Aoun, E. Baubion, C. Derancourt
Le virus Zika (ZIKV), initialement identifié en 1947, est un Flavivirus ré-émergent, principalement transmis par les piqûres de moustiques du genre Aedes. Jusqu'aux récentes épidémies dans les îles du Pacifique et en Amérique centrale et du sud, il était réputé à l'origine d'une maladie bénigne, asymptomatique dans la majorité des cas, ou avec des symptômes modérés non spécifiques (fièvre, éruption, conjonctivite, arthralgies…). Au cours de l'épidémie actuelle, d'une ampleur inédite, de nouveaux modes de transmission (transfusionnel, périnatal, sexuel) et des complications neurologiques sévères telles que des malformations congénitales chez les fœtus de mères infectées et des syndromes de Guillain-Barré chez l'adulte ont été mis en évidence. Cette situation, dans un contexte de potentielle pandémie mondiale à venir, a amené l'Organisation mondiale de la santé (OMS) à déclarer l'infection à ZIKV urgence de santé publique de portée internationale en février 2016.Zika Virus (ZIKV), originally identified in 1947, is a re-emerging Flavivirus transmitted mainly through bites by Aedes mosquitos. Until the recent outbreaks in the Pacific islands and Central and South America, it was known to cause benign disease, in most cases asymptomatic or with mild and nonspecific symptoms (fever, rash, conjunctivitis, arthralgia, etc.). The unprecedented current epidemic has highlighted new modes of transmission (through blood, perinatally and sexually) as well as serious neurological complications such as congenital defects in the fetuses of infected mothers and Guillain-Barre syndrome in adults. This situation, coupled with the threat of worldwide spread, prompted the WHO to declare the ZIKV a public health emergency of international concern in February 2016.



http://ift.tt/2tbP46I

When cancer patients suddenly have a positive pregnancy test

We present the case of non-small cell lung cancer (NSCLC) in a 48-year-old woman with an active history of smoking. The patient initially presented to her general practitioner with a progressive swelling on the neck. Further investigations diagnosed a metastatic lung tumour, and palliative chemotherapy was started. After 5 months of treatment, by newly reported amenorrhoea, cautiously before a restaging CT scan of the abdomen, a pregnancy test was performed and was positive. Both the gynaecological examination and the hormonal panel yielded no signs of pregnancy. Immunohistochemically, staining of the tumour was strongly positive for β-subunit of human chorionic gonadotropin (β-hCG) suggesting that the tumour was responsible for high β-hCG levels.

Paraneoplastic β-hCG secretion from adenocarcinomas is rare. In the literature, only a few such cases have been reported. Previous studies suggested that the ability to secrete β-hCG in tumours may correlate to some extent to chemoresistance and thus, to a worse prognosis.

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Review of phase III trial data on IL-23 Inhibitors Tildrakizumab and Guselkumab for psoriasis

Abstract

Background

The development of monoclonal antibodies targeting IL-12 and IL-23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL-23 alone plays a role in the pathogenesis of psoriasis.

Objective

The objective was to review the phase III clinical trial data for the anti-IL-23 agents in order to evaluate the safety and efficacy profile of each agent.

Methods

We reviewed the results of the phase III clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab. The results of phase III trials on risankizumab have not yet been reported.

Results

By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was greater than 60% among the most efficacious dose of each agent. The percentage of patients achieving PASI 90 at week 16 was the primary endpoint for the phase III trials for guselkumab, which was above 70%. The safety profiles of the agents were comparable, with the most commonly reported adverse events of nasopharyngitis and upper respiratory tract infections.

Conclusion

The anti-IL-23 agents demonstrated a rapid clinical improvement that is similar or superior to the improvement seen with currently marketed IL-17 inhibitors with a favorable short-term safety profile. The results of the phase III trials support the notion that IL-23 is a potential target in psoriasis treatment.

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