Πέμπτη 5 Νοεμβρίου 2020

Overexpression of Fgf8 in the epidermis inhibits hair follicle development

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Abstract

The hair follicle is a classical model for studying epithelial‐mesenchymal interactions. Given the critical role of fibroblast growth factor 8 (Fgf8) in embryonic development, we generated a mouse model that overexpresses Fgf8 specifically in the epidermis. Interestingly, these mutant mice exhibited stunted, smaller bodies and severe hypotrichosis. Histological analysis showed that the hair follicles in the mutants were arrested at stage 2 of hair development. The density of hair follicles in the mutant mice was also lower compared to that in the control mice. Overexpression of Fgf8 inhibited the proliferation of epidermal cells and simultaneously promoted apoptosis, leading to the arrest of hair follicle development. Further analysis showed that sonic hedgehog (Shh) and bone morphogenetic protein 4 (Bmp4) were downregulated and upregulated, respectively. To summarize, our study demonstrates that FGF signaling plays an important role in the regulation of hair folli cle development.

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Paracrine roles of hormone receptors in Riehl’s melanosis: A quantitative analysis of estrogen and progesterone receptor expression patterns

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Abstract

The incidence of Riehl's melanosis (RM) is most common in the fifth or sixth decade of life with a female preponderance. As the skin is regarded a non‐reproductive organ on which sex steroid hormones act, a possible relationship between the pathogenesis of RM and sex steroid hormone receptors can be inferred. This study intended to evaluate the expression profile of estrogen receptor (ER)β and progesterone receptor (PR) in RM. Twelve lesional and perilesional normal‐appearing skin samples of RM patients and the skin of 12 healthy controls were retrieved for analysis. Real‐time PCR analysis and immunohistochemical studies were conducted for ER β and PR, respectively. The lesional and perilesional normal‐appearing skin of 12 patients with RM and the skin of 12 healthy controls were retrieved for analysis. Interestingly, the dermal ERβ immunostaining intensity was increased more in lesional skin than in perilesional skin. When compared to healthy controls, increased expr ession of ERβ and PR mRNAs was observed in the lesional skin of patients with RM. Of note, epidermal and dermal ERβ and dermal PR expressions showed increased staining intensities in the lesional skin of RM patients compared to healthy controls. The altered expression of ERβ and PR in RM supports the possible role of these hormone receptors in the pathogenesis of RM.

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Far-Lateral Transcondylar Approach to a Right Cervicomedullary Dural Arteriovenous Fistula of the Posterior Fossa

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0040-1705162

Objectives Dural arteriovenous fistulas (DAVFs) at the cervicomedullary junction are uncommon and often accompanied by subarachnoid hemorrhage (SAH). We aim to illustrate in detail the microsurgical procedure for treating a DAVF located at the cervicomedullary junction. Design We present a two-dimensional operative video that includes clinical history, preoperative imaging, surgical strategy, still images with labels, clinical course, and postoperative imaging. Setting The microsurgery was performed at an academic medical center. Participant The patient is a 55-year-old female who presented with SAH, acute onset headache, nausea, and vomiting. Angiography demonstrated right vertebral artery vasospasm and a persistent arteriovenous shunt at the cervicomedullary junction supplied by small perforating arteries of the right vertebrobasilar junction (Fig. 1). Main Outcome Measures The patient was placed in the park-bench position with the head turned to the contralateral side. A hockey stick incision was made, followed by a right-side far-lateral transcondylar approach. Indocynanine green videoangiography was performed to help identify the areas of arteriovenous shunting. Multiple clips were placed to interrupt vessels that corresponded to arterial feeders at the level of the C1 and C2 nerve root sleeves (Fig. 2). The dura was closed in a water tight fashion and the posterior fossa was reconstructed with a titanium mesh. Results Postoperative imaging showed no evidence of continued arteriovenous shunting. The patient was discharged in good clinical condition with an uneventful postoperative course. Conclusion A deep understanding of the microsurgical vascular anatomy is necessary for successful occlusion of a cervicomedullary DAVF.The link to the video can be found at: https://youtu.be/-LfOcNB05BY.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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A collaborative care psychosocial intervention to improve late life depression in socioeconomically deprived areas of Guarulhos, Brazil: the PROACTIVE cluster randomised controlled trial protocol

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The elderly population has been growing in most low- and middle-income countries (LMIC), and depression is a common condition among these populations. The lack of integration between mental health and primary ...
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Effect of radiotherapy after breast-conserving surgery in elderly patients with early breast cancer according to the AJCC 8th Edition Breast Cancer Staging System in Japan.

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CONCLUSIONS: RT was associated with significantly improved RFS, but had no significant impact on OS in elderly patients with breast cancer after BCS. Adjuvant RT should be performed even for elderly patients with early breast cancer. PMID: 33141399 [PubMed - as supplied by publisher] (Source: Breast Cancer)
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Optimal, Large-Scale Propagation of Mouse Mammary Tumor Organoids

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AbstractTumor organoids mimic the architecture and heterogeneity of in vivo tumors and enable studies of collective interactions between tumor cells as well as with their surrounding microenvironment. Although tumor organoids hold significant promise as cancer models, they are also more costly and labor-intensive to cultivate than traditional 2D cell culture. We sought to identify critical factors regulating organoid growth ex vivo, and to use these observations to develop a more efficient organoid expansion method. Using time-lapse imaging of mouse mammary tumor organoids in 3D culture, we observed that outgrowth potential varies non-linearly with initial organoid size. Maximal outgrowth occurred in organoids with a starting size between ~10 to 1000 cells. Based on these observations, we ...
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Characterization of Organoid Cultures to Study the Effects of Pregnancy Hormones on the Epigenome and Transcriptional Output of Mammary Epithelial Cells

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AbstractThe use of mouse derived mammary organoids can provide a unique strategy to study mammary gland development across a normal life cycle, as well as offering insights into how malignancies form and progress. Substantial cellular and epigenomic changes are triggered in response to pregnancy hormones, a reaction that engages molecular and cellular changes that transform the mammary epithelial cells into "milk producing machines". Such epigenomic alterations remain stable in post-involution mammary epithelial cells and control the reactivation of gene transcription in response to re-exposure to pregnancy hormones. Thus, a system that tightly controls exposure to pregnancy hormones, epigenomic al terations, and activation of transcription will allow for a better understanding of such...
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Polycythämia vera in der differenzialdiagnostischen Abklärung kognitiver Defizite

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Dtsch Med Wochenschr 2020; 145: 1625-1627
DOI: 10.1055/a-1219-9564

Anamnese Es erfolgt die Aufnahme einer 82-jährigen Patientin zur weiteren Abklärung zunehmender kognitiver Defizite und Gangunsicherheit. Diagnostik und Befunde In der durchgeführten Computertomografie des Kopfes zeigten sich die Zeichen einer fortgeschrittenen subkortikalen arteriosklerotischen Enzephalopathie (SAE). Laborchemisch fiel ein erhöhter Hämoglobinwert von 19,9 g/dl auf. Bei zusätzlicher Mutation in der JAK-2-Analyse wurde die Diagnose einer Polycythämia vera (Pv) gestellt. Nach Aderlass-Therapie zeigte sich eine Verbesserung der Kognition. Diskussion Die progredienten kognitiven Defizite sind bei vorbestehender SAE im Zusammenhang mit der neu diagnostizierten Pv zu sehen. Nach entsprechender Therapie der Pv ist auch langfristig eine Besserung der Kognition zu beobachten, sodass in diesem Fallbericht die Wichtigkeit einer Abklärung sekundärer, potenziell behandelbarer Ursachen von kognitiven Defiziten hervorgehoben wird.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Magnesium: Bedeutung für die hausärztliche Praxis – Positionspapier der Gesellschaft für Magnesium-Forschung e. V.

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Dtsch Med Wochenschr 2020; 145: 1628-1634
DOI: 10.1055/a-1166-7229

In der Bevölkerung und vor allem bei Risikogruppen muss mit Magnesiummangel gerechnet werden. Magnesiummangel kann zahlreiche Symptome verursachen, ist per se pathologisch und deshalb therapiebedürftig. Die Diagnostik stützt sich auf die klinische Symptomatik in Verbindung mit anamnestischen Hinweisen und Laborparametern. Eine schlechte Magnesiumversorgung ist mit einem erhöhten Risiko für zahlreiche Erkrankungen assoziiert, darunter metabolisches Syndrom, Diabetes mellitus Typ 2 und Herz-Kreislauf-Erkrankungen. Magnesiummangel tritt häufig auch als Komorbidität auf und kann zur Exazerbation von Krankheiten beitragen. Magnesium sollte eine größere Aufmerksamkeit geschenkt werden, um Mangelzustände als Ursache vielfältiger Symptome sowie als Risikofaktor für Erkrankungen zu vermeiden. Eine Optimierung der Magnesiumversorgung kann einen wichtigen Beitrag in der Prävention leisten. Die orale Magnesiumtherapie ist unbedenklich und kostengünstig.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Can propranolol act as a chemopreventive agent during oral carcinogenesis? An experimental animal study

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The multistep process of oral carcinogenesis provides a biological rationale for the use of chemoprevention in individuals at increased risk of developing oral cancer. We aimed to determine if low doses of propranolol can prevent the development of oral cancer using a tobacco-relevant and p53-associated animal model of cancer initiation. Twenty-six Wistar rats were randomly allocated into two groups, vehicle, and propranolol. All animals received 4-nitroquinoline N-oxide (4NQO) at 25 ppm diluted in the drinking water for 20 weeks. Animals from the propranolol group received propranolol (0.1 mg/kg) 5 days per week by gavage for 18 weeks. The clinical analysis was performed by measuring the area of the lesion and assessment of scores based on lesion appearance (papule; plaque ; nodule or ulcerated). Histopathological analysis was performed to determine the presence of epithelial dysplasia or invasive squamous cell carcinoma (SCC). The average lesion area in 4NQO + vehicle and in 4NQO + propranolol groups were 0.20  and 0.28 mm2, respectively (P = 0.53). The percentage of cases clinically graded as papules, thick plaques, nodular areas, and ulcerated lesions was similar between groups (P = 0.94). Histopathological diagnosis also did not differ between groups (P = 0.65), with 54.5 and 70% of cases being diagnosed as SCC in 4NQO and in 4NQO + propranolol groups, respectively. In conclusion, daily doses propranolol at 0.1 mg/kg were not as effective as a chemopreventive therapy in an animal model of 4NQO-induced carcinogenesis. * Dr. Vivian P. Wagner and Dr. Tobias R. Spuldaro contributed equally to the writing of this article. Received 8 June 2020 Accepted 24 July 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.eurjcancerprev.com). Correspondence to Vivian Petersen Wagner, Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Av. Limeira, 901, Piracicaba, São Paulo, Brazil, Tel: +55 19 2106 5213; e-mail: vivianpetersen@hotmail.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer

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Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by ...
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LncRNA SNHG3, a potential oncogene in human cancers

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Long noncoding RNAs (lncRNAs) are composed of > 200 nucleotides; they lack the ability to encode proteins but play important roles in a variety of human tumors. A large number of studies have shown that dysreg...
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