Monoubiquitination of histone H2B on lysine 120 (H2Bub1) is an epigenetic mark generally associated with transcriptional activation, yet the global functions of H2Bub1 remain poorly understood. Ferroptosis is a form of non‐apoptotic cell death characterized by the iron‐dependent overproduction of lipid hydroperoxides, which can be inhibited by the antioxidant activity of the solute carrier family member 11 (SLC7A11/xCT), a component of the cystine/glutamate antiporter. Whether nuclear events participate in the regulation of ferroptosis is largely unknown. Here, we show that the levels of H2Bub1 are decreased during erastin‐induced ferroptosis and that loss of H2Bub1 increases the cellular sensitivity to ferroptosis. H2Bub1 epigenetically activates the expression of SLC7A11. Additionally, we show that the tumor suppressor p53 negatively regulates H2Bub1 levels independently of p53's transcription factor activity by promoting the nuclear translocation of the deubiquitinase USP7. Moreover, our studies reveal that p53 decreases H2Bub1 occupancy on the SLC7A11 gene regulatory region and represses the expression of SLC7A11 during erastin treatment. These data not only suggest a noncanonical role of p53 in chromatin regulation but also link p53 to ferroptosis via an H2Bub1‐mediated epigenetic pathway. Overall, our work uncovers a previously unappreciated epigenetic mechanism for the regulation of ferroptosis.
In recent years, uses of environment friendly and biodegradable natural insecticides of plant origin have received renewed attention as agents for vector control. The aim of this research was to determine larvicidal activity of the essential oil derived from roots of Saussurea lappa (Compositae) and the isolated constituents against the larvae of the Culicidae mosquito Aedes albopictus. Essential oil of S. lappa roots was obtained by hydrodistillation and analyzed by gas chromatography (GC) and GC-mass spectrometry (MS). A total of 39 components of the essential oil of S. lappa roots were identified. The essential oil has higher content of (79.80%) of sesquiterpenoids than monoterpenoids (13.25%). The principal compounds in S. lappa essential oil were dehydrocostus lactone (46.75%), costunolide (9.26%), 8-cedren-13-ol (5.06%), and α-curcumene (4.33%). Based on bioactivity-directed fractionation, dehydrocostus lactone and costunolide were isolated from S. lappa essential oil. Dehydrocostus lactone and costunolide exhibited strong larvicidal activity against A. albopictus with LC(50) values of 2.34 and 3.26 μg/ml, respectively, while the essential oil had an LC(50) value of 12.41 μg/ml. The result indicated that the essential oil of S. lappa and the two isolated constituents have potential for use in control of A. albopictus larvae and could be useful in search of newer, safer and more effective natural compounds as larvicides.
The findings of meta-analyses regarding surgical versus non-surgical treatment for acute Achilles tendon rupture are inconsistent. According to this systematic review of overlapping meta-analyses, the current best available evidence suggests that centers offering functional rehabilitation may prefer non-surgical intervention. Surgical treatment may be preferred at centers that do not have functional rehabilitation.
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