Soluble epoxide hydrolase inhibitor, TPPU, attenuates progression of atherosclerotic lesions and vascular smooth muscle cell phenotypic switching.

Atherosclerosis manifests as a chronic inflammation resulting from multiple interactions between circulating factors and various cell types in blood vessel walls. Growing evidence shows that phenotypic switching and proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the progression of atherosclerosis. Soluble epoxide hydrolase (sEH)/epoxyeicosatrienoic acids are mediated by vascular inflammation. N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl]-urea (TPPU) is an sEH inhibitor. This study investigated the therapeutic effect of TPPU on atherosclerosis in vivo and homocysteine-induced vascular inflammation in vitro and explored their molecular mechanisms. We found that TPPU decreased WD-induced atherosclerotic plaque lesions, inflammation, expression of sEH, and nicotinamide adenine dinucleotide phosphate oxidase-4 (Nox4), and increased the expression of contractile phenotype marker of aortas in ApoE (-/-) mice. TPPU also inhibited homocysteine-stimulated VSMC proliferation, migration, and phenotypic switching, and reduced Nox4 in human-aorta-VSMC regulation. We conclude that TPPU has anti-atherosclerotic effects, potentially because of the suppression of VSMC phenotype switching. Thus, TPPU could be a potential therapeutic target for phenotypic switching attenuation in atherosclerosis.

Preventive Effects of Chrysanthemum coronarium L. Extract on Bone Metabolism In Vitro and In Vivo.

Osteoporosis is characterized by decreased bone mass and bone microarchitectural failure, leading to an enhanced risk of bone fractures. Chrysanthemum coronarium L. (CC) is a natural plant with powerful antioxidant activity. This study investigated the antiosteoporotic effects of CC extracts in in vitro cell cultures and in vivo bone loss animal models. CC stimulated osteoblast differentiation and mineralized bone formation by osteoblasts by increasing the expression of bone formation markers (alkaline phosphatase, osteoprotegerin, and osteoprotegerin/receptor activator nuclear factor-κB ligand ratio) in the murine preosteoblastic cell line MC3T3-E1. Additionally, CC was found to inhibit osteoclast differentiation by downregulating bone resorption markers (tartrate-resistant acid phosphatase, cathepsin K, dendritic cell-specific transmembrane protein, and calcitonin receptor) in the murine macrophage-like cell line RAW264.7. CC prevented ovariectomy-induced bone loss, preserved trabecular microarchitecture, and improved serum bone turnover markers in an osteoporotic mouse model. These findings suggest that CC extract may be considered as a natural therapeutic or preventive agent for osteoporotic bone loss.

Old-age-onset subconjunctival juvenile xanthogranuloma without limbal involvement.

BACKGROUND: Juvenile xanthogranuloma (JXG) is a benign idiopathic cutaneous granulomatous tumor occurring primarily in infants less than 1 year old, and less commonly found in older children and adults. To date, however, there have been no reports of patients aged >50 years with cornealscleral JXG without limbal involvement. We describe here a 58-year-old woman with subconjunctival JXG without limbal involvement. CASE PRESENTATION: A 58-year-old female was referred for evaluation of a subconjunctival mass in her left eye, found incidentally 2 weeks earlier. Examination revealed a protruding yellow-orange subconjunctival mass just below the 6-o'clock limbus of her left eye, measuring 6.0 × 4.5 mm, but not extending into the cornea. The overlying conjunctival epithelium was intact, and a feeding vessel was observed between the mass and the episclera. The subconjunctival lesion was excised under local anesthesia, by dissecting the mass from the overlying conjunctiva and underlying sclera. The conjunctiva was reattached to the sclera without creating a bare area. Hematoxylin and eosin-stained sections showed that the mass was a mixed inflammatory lesion containing dense infiltrations of epithelioid histiocytes with foamy cytoplasm, lymphocytes, and plasma cells, as well as multinucleated Touton giant cells with the characteristic circumferential ring of nuclei. Immunohistochemical staining showed that the lesion was positive for the macrophage marker CD68 and negative for the Langerhans cell markers S-100 protein and CD1a, indicating that the lesion was a xanthogranuloma. The patient has been followed up for 12-months without recurrence. CONCLUSIONS: JXG can occur as a solitary subconjunctival mass even in older adults, and immunohistochemistry is useful in differential diagnosis. Simple excision with careful dissection may be effective for subconjunctival JXG.