Metagenomic studies show that diverse resident viruses inhabit the healthy gut; however, little is known about the role of these viruses in the maintenance of gut homeostasis. We found that mice treated with antiviral cocktail displayed more severe dextran sulfate sodium (DSS)-induced colitis compared with untreated mice. DSS-induced colitis was associated with altered enteric viral abundance and composition. When wild-type mice were reconstituted with Toll-like receptor 3 (TLR3) or TLR7 agonists or inactivated rotavirus, colitis symptoms were significantly ameliorated. Mice deficient in both TLR3 and TLR7 were more susceptible to DSS-induced experimental colitis. In humans, combined TLR3 and TLR7 genetic variations significantly influenced the severity of ulcerative colitis. Plasmacytoid dendritic cells isolated from inflamed mouse colon produced interferon-β in a TLR3 and TLR7-dependent manner. These results imply that recognition of resident viruses by TLR3 and TLR7 is required for protective immunity during gut inflammation.
BackgroundAlopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA), a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo.Methodology/ Principal FindingsTopical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP). VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX), a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl2 also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice.Conclusions/ SignificanceOur findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth.
[Purpose] The purpose of this study was to investigate the concurrent validity and
test-retest reliability of the recently introduced OPTOGait Photoelectric Cell System for
the assessment of spatio-temporal parameters of gait. [Subjects] Twenty healthy young
adults (mean age = 27.35, SD = 7.4) were asked to walk 3 times on walkway at a comfortable
speed. [Methods] Concurrent validity was assessed by comparing data obtained using the
OPTOGait and GAITRite systems, and reliability was assessed by comparing data from the
first and third OPTOGait sessions. [Results] Concurrent validity, as identified by
intra-class correlation coefficients (ICC (2, 1) = 0.929–0.998), coefficients of variation
(CVME = 0.32–11.30%), and 95% limits of agreement, showed high levels of
correlation. In addition, the test-retest reliability of the OPTOGait Photoelectric Cell
System was demonstrated as showing a high level of correlation with all spatio-temporal
parameters by intra-class correlation coefficients (ICC (3, 1) = 0.785–0.952),
coefficients of variation (CVME = 1.66–4.06%), 95% limits of agreement,
standard error of measurement (SEM = 2.17–5.96%), and minimum detectable change
(MDC95% = 6.01–16.52%). [Conclusion] The OPTOGait Photoelectric Cell System
has strong concurrent validity along with relative and absolute test-retest reliabilities.
This portable system with easy-to-use features can be used for clinical assessments or
research purposes as an objective means of assessing gait.
There is considerable debate in the management of almost every complication of cholesteatoma. Multicentric studies to compare the efficacies of various treatment modalities are the need of the hour to come to definitive conclusions regarding the best treatment options.
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