Natural Product Based 6-Hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium Scaffold as A New Antifungal Template

Synthetic analogues of the marine-derived class of natural products phloeodictines have been prepared and exhibited potent in vitro fungicidal activities against a broad array of fungal pathogens including drug resistant strains. The 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium structural moiety with a C12 to C16 aliphatic side chain at C-6 has been shown to be the antifungal pharmacophore and may serve as a new antifungal template for further lead optimization.     

Abscess mimicking pre-cervical and submandibular cystic hygroma in a newborn

Pre-cervical inflammation is rarely seen in a newborn. Those swellings that are seen are usually congenital, such as vascular malformations, teratoma, dermoid cyst, thyroglossal cyst, cystic hygroma (abnormal lymphatic tissue), and very rarely, inflammation secondary to infection. Being able to differentiate between each condition is important because the course, treatment and prognosis for each condition are different. This case of a neck abscess in a newborn is reported due to its resemblance to cystic hygroma and highlights the similarities between the two conditions.     

A high-content morphological screen identifies novel microRNAs that regulate neuroblastoma cell differentiation

Neuroblastoma, the most common extracranial solid tumor of childhood, arises from neural crest cell precursors that fail to differentiate. Inducing cell differentiation is an important therapeutic strategy for neuroblastoma. We developed a direct functional high-content screen to identify differentiation-inducing microRNAs, in order to develop microRNA-based differentiation therapy for neuroblastoma. We discovered novel microRNAs, and more strikingly, three microRNA seed families that induce neuroblastoma cell differentiation. In addition, we showed that microRNA seed families were overrepresented in the identified group of fourteen differentiation-inducing microRNAs, suggesting that microRNA seed families are functionally more important in neuroblastoma differentiation than microRNAs with unique sequences. We further investigated the differentiation-inducing function of the microRNA-506-3p/microRNA-124-3p seed family, which was the most potent inducer of differentiation. We showed that the differentiation-inducing function of microRNA-506-3p/microRNA-124-3p is mediated, at least partially, by down-regulating expression of their targets CDK4 and STAT3. We further showed that expression of miR-506-3p, but not miR-124-3p, is dramatically upregulated in differentiated neuroblastoma cells, suggesting the important role of endogenous miR-506-3p in differentiation and tumorigenesis. Overall, our functional screen on microRNAs provided the first comprehensive analysis on the involvements of microRNA species in neuroblastoma cell differentiation and identified novel differentiation-inducing microRNAs. Further investigations are certainly warranted to fully characterize the function of the identified microRNAs in order to eventually benefit neuroblastoma therapy.