SummaryHow the eye forms has been one of the fundamental issues in developmental biology. The retinal anlage first appears as the optic vesicle (OV) evaginating from the forebrain. Subsequently, its distal portion invaginates to form the two-walled optic cup, which develops into the outer pigmented and inner neurosensory layers of the retina. Recent work has shown that this optic-cup morphogenesis proceeds as a self-organizing activity without any extrinsic molecules. However, intrinsic factors that regulate this process have not been elucidated. Here we show that a LIM-homeobox gene, Lhx1, normally expressed in the proximal region of the nascent OV, induces a second neurosensory retina formation from the outer pigmented retina when overexpressed in the chicken OV. Lhx2, another LIM-homeobox gene supposed to be involved in early OV formation, could not substitute this function of Lhx1, while Lhx5, closely related to Lhx1, could replace it. Conversely, knockdown of Lhx1 expression by RNA interference resulted in the formation of a small or pigmented vesicle. These results suggest that the proximal region demarcated by Lhx1 expression permits OV development, eventually dividing the two retinal domains.
The effects of hop extracts (Humulus lupulus L.) on histamine release from rat peritoneal mast cells and human basophilic KU812 cells were studied. Hop water extract (HWE) and XAD-4 50% methanol fraction of HWE (MFH) inhibited histamine release from rat mast cells induced by compound 48/80 at concentrations of 100 and 10 m mg/ml, respectively. Almost the same findings were observed with A23187-induced histamine release from KU812 cells. Next, we studied the effects of hop extracts on antigen-induced nasal rubbing and sneezing in sensitized BALB/c mice. HWE caused a significant inhibition of nasal rubbing and sneezing at a dose of 500 mg/kg. MFH also inhibited nasal rubbing and sneezing dose-dependently. A significant difference was observed from 100 mg/kg in nasal rubbing and 200 mg/kg in sneezing. The effects of both extracts became clear after repeated administration. HWE and MFH significantly inhibited both nasal rubbing and sneezing, respectively, after consecutive treatment for 15 d at smaller doses compared with single administration. This finding indicates that the active component of hop is included in MFH, which was absorbed to Amberlite XAD-4 and eluted with 50% methanol. These results clearly demonstrated that hop extracts may be effective in the relief of symptoms of allergic rhinitis.
Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by severe itching and eczematous lesion. In this study, we applied an ointment containing Dermatophagoides farinae body (Dfb) extract repeatedly on the dorsal skin of NC/ Nga mice with barrier disruption to investigate the characteristics of this murine model of human AD. Following repeated topical application of Dfb ointment twice weekly for 2 weeks, the dermatitis score increased gradually, accompanied by an elevation of total immunoglobulin E level in plasma. Topical application of Dfb ointment also caused epidermal hyperplasia and accumulation of inflammatory cells in the lesional skin and increased expression of T-helper (Th) 1/Th2/Th17 cytokines in axillary lymph node cells. Furthermore, increased sprouting of intraepidermal nerve fibres was observed with an increase in the content of nerve growth factor and decrease in that of semaphorin 3A in the lesional skin. These findings suggest that the characteristics in this model were similar to those observed in patients with AD. Interestingly, it was observed for the first time that scratching behaviour increased in a biphasic fashion by topical application of Dfb ointment in addition to an increase in spontaneous scratching behaviour in this model. It is also suggested that further clarifying the underlying mechanisms of scratching behaviour in this model leads not only to elucidating the pathogenesis of AD but also to discovering novel therapeutic drugs for AD.
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