Suppression of the TRIF-dependent signaling pathway of TLRs by epoxomicin.

Toll-like receptors (TLRs) can recognize specific signatures of invading microbial pathogens and activate a cascade of downstream signals to induce the secretion of inflammatory cytokines, chemokines, and type I interferons. The activation of TLRs triggers two downstream signaling pathways: the MyD88- and the TRIF-dependent pathways. To evaluate the therapeutic potential of epoxomicin, a member of the linear peptide α',ß'-epoxyketone first isolated from an actinomycetes strain, we examined its effects on signal transduction via TLR signaling pathways. Epoxomicin inhibited the activation of NF-kB and IRF3 induced by TLR agonists, decreased the expression of interferon-inducible protein-10, and inhibited the activation of NF-kB and IRF3 induced by overexpression of downstream signaling components of TLR signaling pathways. These results suggest that epoxomicin can regulate both the MyD88- and TRIF-dependent signaling pathways of TLRs. Thus, it might have potential as a new therapeutic drug for a variety of inflammatory diseases.

Unusual ocular injury by an acupuncture needle.

PURPOSE: To educate ophthalmologists on the potential dangers of periocular acupuncture and to describe an unusual mechanism of retinal injury. METHODS: A 42-year-old woman who presented with blurred central vision and loss of peripheral vision. Her medical history was significant for hemifacial spasms related to a facial nerve injury, for which she had sought treatment. Clinical examination showed vertically oriented subretinal track measuring 12 mm in length, contiguous to the macula, with normal optic nerve appearance and foveal reflexes. Spectral domain optical coherence tomography showed a full-thickness perforation of the neurosensory retina at the inferior retinal arcade. Visual field testing 3 weeks after her injury showed 90% loss of her nasal hemifield. Electroretinography performed 8 weeks postinjury showed a 50% decrease in the right B-wave. Multifocal electroretinography showed a mild decrease in the recording of the right eye versus that of the left eye. CONCLUSION: Based on the history and clinical findings, the acupuncture needle penetrated the inferior globe and created a subretinal track. The particular location of the needle entry into the eye and the extreme malleability of the acupuncture needle created a long subretinal track. Ophthalmologists should be familiar with the ocular injuries caused by periocular acupuncture therapies.