The Henna pigment Lawsone activates the Aryl Hydrocarbon Receptor and impacts skin homeostasis.

As a first host barrier, the skin is constantly exposed to environmental insults that perturb its integrity. Tight regulation of skin homeostasis is largely controlled by the aryl hydrocarbon receptor (AhR). Here, we demonstrate that Henna and its major pigment, the naphthoquinone Lawsone activate AhR, both in vitro and in vivo. In human keratinocytes and epidermis equivalents, Lawsone exposure enhances the production of late epidermal proteins, impacts keratinocyte differentiation and proliferation, and regulates skin inflammation. To determine the potential use of Lawsone for therapeutic application, we harnessed human, murine and zebrafish models. In skin regeneration models, Lawsone interferes with physiological tissue regeneration and inhibits wound healing. Conversely, in a human acute dermatitis model, topical application of a Lawsone-containing cream ameliorates skin irritation. Altogether, our study reveals how a widely used natural plant pigment is sensed by the host receptor AhR, and how the physiopathological context determines beneficial and detrimental outcomes.

Endoscopic ultrasound-guided radiofrequency ablation of the pancreas: An experimental study with pathological correlation.

BACKGROUND: The treatment of pancreatic cancer represents a major objective in clinical research, as it still remains the fourth leading cause of cancer deaths among men and women, with approximately 6% of all cancer-related deaths. MATERIALS AND METHODS: We studied the assessment of an endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) probe through a 19G needle in order to achieve a desirable necrosis area in the pancreas. Radiofrequency ablation of the head of the pancreas was performed on 10 Yorkshire pigs with a weight between 25 kg and 35 kg and a length of 40-70 cm. Using an EUS-guided RFA experimental probe, we ablated an area of 2-3 cm width. The biological samples were harvested after 3 days and 5 days and necropsy was performed 1 week after the procedure. RESULTS: All pigs showed no significant change regarding their behavior and no signs of complication was encountered. Blood analysis revealed increased values of amylase, alkaline phosphatase, and gamma-glutamyl transpeptidase on the 3rd day but a decrease on the 5th day. After necropsy and isolation of the pancreas, the ablated area was easily found, describing a solid necrosis. The pathological examination revealed a coagulative necrosis area with minimal invasion and inflammatory tissue at about 2 cm surrounding the lesion. CONCLUSION: EUS-RFA is a feasible technique and might represent a promising therapy for the future treatment of pancreatic cancer. However, further studies are necessary to investigate EUS-guided RFA as an option for palliation in pancreatic cancer until it can be successfully used in human patients.