p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells.

Chromatin structural states and their remodelling, including higher-order chromatin folding and three-dimensional (3D) genome organisation, play an important role in the control of gene expression. The role of 3D genome organisation in the control and execution of lineage-specific transcription programmes during the development and differentiation of multipotent stem cells into specialised cell types remains poorly understood. Here, we show that substantial remodelling of the higher-order chromatin structure of the epidermal differentiation complex (EDC), a keratinocyte lineage-specific gene locus on mouse chromosome 3, occurs during epidermal morphogenesis. During epidermal development, the locus relocates away from the nuclear periphery towards the nuclear interior into a compartment enriched in SC35-positive nuclear speckles. Relocation of the EDC locus occurs prior to the full activation of EDC genes involved in controlling terminal keratinocyte differentiation and is a lineage-specific, developmentally regulated event controlled by transcription factor p63, a master regulator of epidermal development. We also show that, in epidermal progenitor cells, p63 directly regulates the expression of the ATP-dependent chromatin remodeller Brg1, which binds to distinct domains within the EDC and is required for relocation of the EDC towards the nuclear interior. Furthermore, Brg1 also regulates gene expression within the EDC locus during epidermal morphogenesis. Thus, p63 and its direct target Brg1 play an essential role in remodelling the higher-order chromatin structure of the EDC and in the specific positioning of this locus within the landscape of the 3D nuclear space, as required for the efficient expression of EDC genes in epidermal progenitor cells during skin development.

Less correction with minimally invasive surgery for adolescent idiopathic scoliosis compared to open surgical correction.

Purpose: In this study, we investigated the relationship between the results of thoracic curve correction using minimally invasive surgeries in 35 patients and open surgical correction in 47 patients with adolescent idiopathic scoliosis. Methods: The correlations between the Cobb's angle of the primary and postoperative curves, angle of thoracic kyphosis and lumbar lordosis, correction percentage, derotation values, estimated blood loss, duration of surgery, and period of hospitalization after surgery were assessed by calculating the mean and standard deviation. Calculation and comparison were performed using Pearson correlation. Results: The Cobb's angle correction ranged from 53.4° ± 11.8° to 6.7° ± 5.2° (p < 0.001) in the open surgical correction group and from 51.2° ± 11.4° to 11.7° ± 5.8° (p < 0.001) in the minimally invasive surgery group before and after surgery, respectively. The percentage of curvature correction was 88.2% ± 8.0% and 77.7% ± 10.7% (p < 0.001) in the open surgical correction and minimally invasive surgery groups, respectively. The estimated blood loss was higher in the open surgical correction group than in the minimally invasive surgery group (208.7 ± 113.4 vs 564.3 ± 242.7 mL). Axial rotation was changed from 29.1°± 7.5 to 17.1°± 6.8 (p < 0.001) in the open surgical correction group and from 28.9°± 7.8 to 19.4°± 6.4 (p < 0.001) in the minimally invasive surgery group. The duration of surgery was shorter in the open surgical correction group than in the minimally invasive surgery group (266.6 ± 64.3 vs 346.2 ± 70.5 min). A positive correlation between time of operation and Cobb's angle correction (in °) in open surgical correction (r = 0.37) and minimally invasive surgery (r = 0.43) was found. Conclusion: The open surgical correction procedures were more effective than minimally invasive surgery in correcting the spinal curve. The increase in the duration of open surgical correction increases the estimated blood loss, but it also more significantly improves the correction of Cobb's angle. Level of evidence: III.

Calcitonin gene-related peptide (CGRP) may award relative protection from interferon-γ-induced collapse of human hair follicle immune privilege.

Interferon-γ (IFNγ)-induced collapse of hair follicle (HF) immune privilege (IP) is a key element in the pathogenesis of alopecia areata. In this pilot study, we investigated whether the immunosuppressive neuropeptide, calcitonin gene-related peptide (CGRP), can protect from and/or restore IFNγ-induced HF-IP collapse. After showing that human scalp HFs express CGRP receptor-like receptor (CRLR) immunoreactivity, anagen HFs were cultured in the presence of IFNγ, with CGRP added before or after. Adding CGRP after IFNγ administration ('restoration assay') failed to downregulate IFNγ-induced ectopic MHC class I expression, while MHC class II expression was reduced. However, administering CGRP before IFNγ application ('protection assay') significantly reduced the IFNγ-induced overexpression and ectopic expression of MHC class I and II and reduced the increased degranulation of perifollicular mast cells induced by IFNγ. This suggests that CGRP may not restore HF-IP once it has collapsed, but may protect it from collapsing. Therefore, CRLR stimulation might help to retard AA progression.

Serum Antibody Ig G and Ig M Titers for Opisthorchis felineus Correlate with Eggs in Faeces--a Comprehensive Study in Chuvash Republic, Russia.

The Cholangiocarcinoma is a. The risk of development of cholangiocarcinoma, generally a rare type of a liver tumor, increases during infection of Opisthorchiasis. For this reason the timely detection of Opisthorchiasis is important for Cholangiocarcinoma prevention. There are many studies which concern the detection of pathogenesis of Opisthorchis viverrini infection but a little known about Opisthorchis felineus. In this study we investigate a correlation of the eggs which are found in a faeces and are comparable with a serum Ig G and Ig M antibody level that were detected with ELISA test in a large group of patients. The result is showing positive correlation between evidence of the Opisthorchis felineus eggs that were found in a faeces and antibody Ig G and Ig M level in a serum. Moreover the combination of two methods can improve the Opisthorchiasis diagnostic: the serum antibody and faeces investigation of eggs.

Expression of estrogen receptor-alpha, glucocorticoid receptor, beta-catenin and glycogen synthase kinase-3beta in the uterus of mice following long-term treatment with estrogen and glucocorticoid hormones.

BACKGROUND: It has been shown that long-term glucocporticoid administration to chronically estradiol-treated mice decreases uterine weight, proliferation in all uterine tissues, the number of perpendicularly oriented mitoses in uterine epithelia and the incidence of atypical endometrial hyperplasia. However, mechanisms of chronic glucocorticoid action on estrogen-dependent processes in the uterus are unclear. METHODS AND RESULTS: Results of present research showed that adding of glucocorticoid dexamethasone (in drinking water, 2mg/l) to estradiol-treated mice led to a decrease in the level of glucocorticoid receptor, to an increase in levels of estrogen receptor-alpha, beta-catenin and glycogen synthase kinase-3beta in uterine tissues of ovariectomized mice at 30, 60 and 90 days of the treatment. When vehicle was used instead estradiol, dexamethasone did not produce detectable changes in all parameters tested at all periods of observation. CONCLUSION: Results allow to conclude that estrogen and glucocorticoid receptors, beta-catenin and glycogen synthase kinase-3beta are involved in estrogen-dependent changes in uterine morphology and hyperplasia formation.

Lithium treatment enhances estradiol-induced proliferation and hyperplasia formation in the uterus of mice.

OBJECTIVES: It is suggested that the Wnt/beta-catenin pathway plays a role in the regulation of estrogen action in the uterus. However, this suggestion has not been proved. Lithium can mimic increased activity of the Wnt/beta-catenin pathway by blocking the activity of glycogen synthase kinase-3beta. There are no data on the effects of lithium on estrogen-dependent processes in the uterus. This work was therefore aimed to examine the action of lithium on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments. STUDY DESIGN: Ovariectomized mice received estradiol dipropionate (2 microg per 100g; s.c.) once a week or vehicle and drank tap water with 0.05% lithium chloride or plain tap water for 2 or 30 days. RESULTS: In animals treated with estradiol and lithium for a month, the incidence of atypical endometrial hyperplasia was significantly higher. In animals treated with estradiol and lithium for 2 days or for a month, uterine mass, the number of mitotic cells and BrdU-labelled cells in luminal epithelium, glandular epithelium, stromal and myometrial cells was markedly greater, whereas the levels of estrogen receptors-alpha, beta-catenin and glycogen synthase kinase-3beta were markedly lower in all uterine compartments, than in those in mice received estradiol with no lithium to drink. CONCLUSIONS: Lithium treatment results in an increase in estradiol-induced proliferative and morphogenetic changes in the uterus. This action of lithium is associated with decreased expression of estrogen receptors-alpha, beta-catenin and glycogen synthase kinase-3beta in the uterus.

MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway.

Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting ß-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators ß-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify ß-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging.