Ultrastructural immunocytochemistry suggests that periderm granules in embryonic chick epidermis contain beta-defensins

The capability to express an innate antimicrobial action through the production of beta-defensins in the skin of chick embryos has been studied by immunocytochemistry. The immunolabeling of periderm granules present in the initial embryonic epidermis of the chick is obtained with a lizard anti-defensin antibody (Ac-BD-15) that recognizes a homologous peptide in the chick beta-defensin 9. Similar granules, termed honeycomb granules, are also stored in some basophilic granulocytes of adult and hatchling chicks, but did not show immunoreactivity to the antibody. It is unclear whether this morphology indicates different organelles, content or lack of available antigens due to organelle packaging. The remarkable ultrastructural similarity between periderm granules and the honeycomb granules present in basophil granulocytes further indicates that embryonic keratinocytes can synthesize antimicrobial peptides together with corneous proteins. These peptides may participate in the formation of an epidermal microbial barrier during ontogenesis or protect the embryo in case of damage to the amniotic-periderm barrier. These transient organelles, apart from the early keratinization of the epidermis that forms the initial barrier before hatching may also contribute to the formation of an efficient anti-microbial barrier against the penetration of microbes during embryonic life until hatching when the adaptive immunity system is still immature.     

Chilblain-like lesions in children following suspected COVID-19 infection

During the COVID-19 pandemic, chilblain-like lesions have been reported in mildly symptomatic children and adolescents. We present four children investigated for suspected COVID-19 infection who presented with acral skin findings and mild systemic symptoms. Histology from one case showed signs of vasculitis with evident fibrin thrombus.     

Variants and new entities of bladder cancer

Pathological evaluation of bladder cancer typically reveals great tumour heterogeneity, and therefore the common observation of urothelial carcinoma exhibiting a wide variety of histopathological patterns is not surprising. Some of these patterns are so distinctive that they have been recognised as specific variants of urothelial carcinoma. Classifications have recently been revised in the 2016 World Health Organisation (WHO) classification of tumours of the urinary system and male genital organs. The current WHO classifications clarify terminological issues and provide better definition criteria, but also incorporate some new entities. Many of these variants have important prognostic or therapeutic implications worth knowing by the urologist and oncologist, but also represent diagnostic challenges in daily pathology practice. This review will discuss the features of variants of urothelial carcinoma in the context of our current clinical practice. Histological variations and new entities of bladder cancer not included in the current WHO classification of urothelial tumours will be briefly discussed.     

Melatonin down‐regulates MDM2 gene expression and enhances p53 acetylation in MCF‐7 cells

Compelling evidence demonstrated that melatonin increases p53 activity in cancer cells. p53 undergoes acetylation to be stabilized and activated for driving cells destined for apoptosis/growth inhibition. Over‐expression of p300 induces p53 acetylation, leading to cell growth arrest by increasing p21 expression. In turn, p53 activation is mainly regulated in the nucleus by MDM2. MDM2 also acts as E3 ubiquitin ligase, promoting the proteasome‐dependent p53 degradation. MDM2 entry into the nucleus is finely tuned by two different modulations: the ribosomal protein L11, acts by sequestering MDM2 in the cytosol, whereas the PI3K‐AkT‐dependent MDM2 phosphorylation is mandatory for MDM2 translocation across the nuclear membrane. In addition, MDM2‐dependent targeting of p53 is regulated in a nonlinear fashion by MDM2/MDMX interplay. Melatonin induces both cell growth inhibition and apoptosis in MCF7 breast cancer cells. We previously reported that this effect is associated with reduced MDM2 levels and increased p53 activity. Herein, we demonstrated that melatonin drastically down‐regulates MDM2 gene expression and inhibits MDM2 shuttling into the nucleus, given that melatonin increases L11 and inhibits Akt‐PI3K‐dependent MDM2 phosphorylation. Melatonin induces a 3‐fold increase in both MDMX and p300 levels, decreasing simultaneously Sirt1, a specific inhibitor of p300 activity. Consequently, melatonin‐treated cells display significantly higher values of both p53 and acetylated p53. Thus, a 15‐fold increase in p21 levels was observed in melatonin‐treated cancer cells. Our results provide evidence that melatonin enhances p53 acetylation by modulating the MDM2/MDMX/p300 pathway, disclosing new insights for understanding its anticancer effect.