A novel nonsense mutation of ERCC2 in a Vietnamese family with xeroderma pigmentosum syndrome group D.

Xeroderma pigmentosum (XP) group D, a severe disease often typified by extreme sun sensitivity, can be caused by ERCC2 mutations. ERCC2 encodes an adenosine triphosphate (ATP)-dependent DNA helicase, namely XP group D protein (XPD). The XPD, one of ten subunits of the transcription factor TFIIH, plays a critical role in the nucleotide-excision repair (NER) pathway. Mutations in XPD that affect the NER pathway can lead to neurological degeneration and skin cancer, which are the most common causes of death in XP patients. Here, we present detailed phenotypic information on a Vietnamese family in which four members were affected by XP with extreme sun sensitivity. Genomic analysis revealed a compound heterozygous mutation of ERCC2 that affected family members and single heterozygous mutations in unaffected family members. We identified a novel, nonsense mutation in one allele of ERCC2 (c.1354C > T, p.Q452X) and a known missense mutation in the other allele (c.2048G > A, p.R683Q). Fibroblasts isolated from the compound heterozygous subject also failed to recover from UV-driven DNA damage, thus recapitulating aspects of XP syndrome in vitro. We describe a novel ERCC2 variant that leads to the breakdown of the NER pathway across generations of a family presenting with severe XP.

Anti-inflammatory and wound healing activities of calophyllolide isolated from Calophyllum inophyllum Linn.

Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1ß, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.