Terminal keratinocyte differentiation in vitro is associated with a stable DNA methylome

xlomafota13 shared this article with you from Inoreader Terminal keratinocyte differentiation in vitro is associated with a stable DNA methylome Via Experimental Dermatology Abstract The epidermal compartment of the skin is regenerated constantly by proliferation of epidermal keratinocytes. Differentiation of a subset of these keratinocytes allows the epidermis to retain its barrier properties. Regulation of keratinocyte fate—whether to remain proliferative or terminally differentiate—is complex and not fully understood. The objective of our study was to assess if DNA methylation changes contribute to the regulation of keratinocyte fate. We employed genome-wide MethylationEPIC beadchip array measuring approximately 850 000 probes combined with RNA sequencing of in vitro cultured non-differentiated and terminally differentiated adult human primary keratinocytes. We did not observe a correlation between methylation status and transcriptome changes. Moreover, only two differentially methylated probes were detected, of which one was located in the TRIM29 gene. Although TRIM29 knock-down resulted in lower expression levels of terminal differe ntiation genes, these changes were minor. From these results, we conclude that—in our in vitro experimental setup—it is unlikely that changes in DNA methylation have an important regulatory role in terminal keratinocyte differentiation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Suppressed microRNA‐195‐5p expression in mycosis fungoides promotes tumor cell proliferation

xlomafota13 shared this article with you from Inoreader Suppressed microRNA‐195‐5p expression in mycosis fungoides promotes tumor cell proliferation Via Experimental Dermatology Abstract Background Several cancers, including mycosis fungoides (MF), have reported dysregulation of miR-195-5p. miR-195-5p plays a role in cell cycle regulation in several malignant diseases. Objectives This study aimed to investigate: (a) the expression level of miR-195-5p in lesional MF skin biopsies and (b) the potential regulatory roles of miR-195-5p in MF. Methods Quantitative real-time polymerase chain reaction (RT-qPCR) was used to determine miR-195-5p expression in MF skin biopsies and cell lines. The effect of miR-195-5p and ADP-ribosylation factor-like protein 2 (ARL2) on cell cycle and apoptosis was measured by flow cytometry assays. Changes in ARL2 expression were determined by RT-qPCR and Western blotting (WB). Results We found lower expression levels of miR-195-5p in lesional skin from MF patients compared with non-lesional MF skin and skin from healthy volunteers. Additionally, miR-195-5p showed lower expression levels in the skin from patients with disease progression compared with patients with stable disease. In vitro studies showed that overexpression of miR-195-5p induced a cell cycle arrest in G0G1. Using microarray analysis, we identified several genes that were regulated after miR-195-5p overexpression. The most downregulated gene after miR-195-5p mimic transfection was ARL2. RT-qPCR and WB analyses confirmed downregulation of ARL2 following transfection with miR-195-5p mimic. Lastly, transfection with siRNA against ARL2 also induced a G0G1 arrest. Conclusion Upregulation of miR-195-5p in MF inhibits cycle arrest by downregulation of ARL2. miR-195-5p may thus function as a tumor suppressor in MF and low miR-195-5p expression in lesional MF skin may promote disease progression. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Experimental Dermatology

xlomafota13 shared this article with you from Inoreader Cover Image Via Experimental Dermatology Cover Illustration: The cover image is based on the Review Article Dysregulated epigenetic modifications in psoriasis by Chang Zeng et al.,https://doi.org/10.1111/exd.14332. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anti‐tumor necrosis factor drug responses and skin‐blood DNA methylation age: Relationships in moderate‐to‐severe psoriasis

xlomafota13 shared this article with you from Inoreader Anti‐tumor necrosis factor drug responses and skin‐blood DNA methylation age: Relationships in moderate‐to‐severe psoriasis Via Experimental Dermatology Abstract Studies have examined the utility of DNA methylation as a biomarker of psoriasis treatment responses, but investigations of treatment responses with Skin-Blood DNA methylation age (SkinBloodAge)—a methylation-based measure of health designed using skin tissues—are lacking. Using a HumanMethylation450 BeadChip blood DNA methylation data set from 70 white patients who presented with moderate-to-severe plaque psoriasis and were treated with anti-tumor necrosis factor (TNF) agents in Madrid, Spain, we examined the cross-sectional relationships of SkinBloodAge with anti-TNF treatment responses. Partial responders had a 7.2-year higher mean SkinBloodAge than excellent responders (P = .03). In linear regression models adjusted for chronological age, sex and anti-TNF agents - on average - partial responders had a 2.65-year higher SkinBloodAge than excellent responders (95%CI: 0.44, 4.86, P = .02). This relationship was attenuated in a sensitivity anal ysis adjusting for white blood cells including known T-cell mediators of psoriasis pathophysiology (β = 1.91-years, 95%CI: −0.50, 4.32, P = .12). Overall, our study suggests that partial responders to anti-TNF therapy have higher SkinBloodAges when compared to excellent responders. Although these findings still need to be confirmed more broadly, they further suggest that SkinBloodAge may be a useful treatment response biomarker that can be incorporated with other blood tests before anti-TNF therapy initiation in moderate-to-severe psoriasis patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

IL6R is a target of miR‐197 in human keratinocytes

xlomafota13 shared this article with you from Inoreader IL6R is a target of miR‐197 in human keratinocytes Via Experimental Dermatology Abstract Psoriasis is a chronic inflammatory disorder with cutaneous and systemic manifestations and substantial negative effects on patients' quality of life. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play a role in the pathogenesis of psoriasis. Previously studies, from others and by us, highlighted specific miRNAs that are dysregulated in psoriatic lesions. MicroRNA-197-3p (miR-197) expression is downregulated in psoriatic lesions compared to normal or uninvolved skin in patients with psoriasis. We have previously reported that miR-197 could modulate IL-22 and IL-17 signalling in psoriasis. Herein, we identify additional biochemical targets of miR-197 in psoriasis. We applied a transcriptome-wide biochemical approach, Protein argonaute-2 photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (Ago2 PAR-CLIP), to search for new targets of miR-197 in live keratinocytes, and validated its results using reporter assay and analysin g by Western blot protein levels in cells overexpressing miR-197. Ago2 PAR-CLIP identified biochemical targets of miR-197, including the alpha subunit of the IL-6 receptor (IL6R). This work provides evidence that IL6R in bona-fide biochemical target of miR-197. IL6R is known to be up-regulated in psoriasis and even was considered as a possible therapeutic target. From the present data and our previous studies, it appears that miR-197 is a major regulator of the interaction between immune system cells and keratinocytes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Methylation patterns of cutaneous T‐cell lymphomas

xlomafota13 shared this article with you from Inoreader Methylation patterns of cutaneous T‐cell lymphomas Via Experimental Dermatology Abstract In cutaneous T-cell lymphoma (CTCL), global hypomethylation of the genome and hypermethylation of tumor suppressor genes were detected. Studies show that methylation dysregulation is often a starting point for processes that might lead to malignant transformation. In this review, all data regarding copy-number variations (CNVs) and mutations in main methylation players DNA methyltransferases/TET in CTCL were summarized. An overview of studies on gene-specific hypomethylation and hypermethylation in CTCL, including methylation of microRNA genes, was presented. The possibility of using the methylation pattern in diagnosis and methylation inhibitors in treatment of CTCL was discussed. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Unusual Cervical Lymph Node Metastasis of Papillary Urothelial Carcinoma

xlomafota13 shared this article with you from Inoreader Unusual Cervical Lymph Node Metastasis of Papillary Urothelial Carcinoma Via ear nose throat Ear Nose Throat J. 2021 Jul 29:1455613211036222. doi: 10.1177/01455613211036222. Online ahead of print. ABSTRACT Papillary urothelial carcinoma is aggressive and characterized by frequent metastasis to distant sites at an early stage. Papillary urothelial carcinoma of the urinary bladder usually metastasizes to the local lymph nodes, liver, lungs, bone, and mediastinum. Urogenital tract carcinoma of the head and neck metastasis is uncommon and rarely reported to the cervical lymph nodes. We present a case of cervical lymph node metastasis of papillary urothelial carcinoma of the urinary bladder. PMID:34325542 | DOI:10.1177/01455613211036222 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The regulatory role of the BDNF/TrkB pathway in organ and tissue fibrosis

xlomafota13 shared this article with you from Inoreader The regulatory role of the BDNF/TrkB pathway in organ and tissue fibrosis Via Cellular and Molecular Biology Histol Histopathol. 2021 Jul 30:18368. doi: 10.14670/HH-18-368. Online ahead of print. ABSTRACT Fibrosis across diverse organ systems is one of the leading causes of morbidity and mortality by inducing progressive architectural remodeling and organ dysfunction. Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase receptor B (TrkB) play crucial roles in regulating neural survival, development, function and plasticity in the central and the peripheral nervous system. Previous studies demonstrated that the BDNF/TrkB pathway is widely distributed in different cell types such as neuron, epithelial cell, hepatocyte, and cardiomyocyte. Recently, there is increasing recognition that BDNF and TrkB are also expressed in fibroblasts in different organs. Moreover, growing evidence was obtained regarding the functional roles of BDNF/TrkB signaling in organ and tissue fibrosis. Thus, this review summarizes the basic molecular ch aracteristics of the BDNF/TrkB cascade and the findings of the crucial roles and therapeutic value in organ and tissue fibrosis including pulmonary fibrosis, hepatic fibrosis, renal fibrosis, cardiac fibrosis, bladder fibrosis and skin fibrosis. Small molecule BDNF mimetic and BDNF-related non-coding RNAs are also discussed for developing new therapeutic approaches for fibrotic disorders. PMID:34327702 | DOI:10.14670/HH-18-368 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Angiomyolipoma Originating From the Nasal Vestibule: A Case Report

xlomafota13 shared this article with you from Inoreader Angiomyolipoma Originating From the Nasal Vestibule: A Case Report Via ear nose throat Ear Nose Throat J. 2021 Jul 30:1455613211036241. doi: 10.1177/01455613211036241. Online ahead of print. ABSTRACT Angiomyolipoma is a benign, mesenchymal, hamartomatous lesion often described in the kidney and may be associated with tuberous sclerosis. Nasal angiomyolipoma is an extremely rare tumor with fewer than 20 cases reported in the literature. We report a case of angiomyolipoma arising in the right nasal vestibule in a 68-year-old male with mild, recurrent right-sided epistaxis, and nasal obstruction. With the exception of arterial hypertension, the patient did not have any comorbidities. Gross examination showed a well-circumscribed, lobulated mass. On the microscopic level, it was composed of mature smooth muscle cells, thick-walled blood vessels of varying sizes, and islands of mature adipose tissue. Angiomyolipoma should be considered as a differential diagnosis for unilateral nasal masses, especially those situated in the nasal vestibule. PMID:34328822 | DOI:10.1177/01455613211036241 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Classifying and Predicting Surgical Complications After Laryngectomy: A Novel Approach to Diagnosing and Treating Patients

xlomafota13 shared this article with you from Inoreader Classifying and Predicting Surgical Complications After Laryngectomy: A Novel Approach to Diagnosing and Treating Patients Via ear nose throat Ear Nose Throat J. 2021 Jul 30:1455613211029749. doi: 10.1177/01455613211029749. Online ahead of print. ABSTRACT OBJECTIVES: The total laryngectomy is one of the most standardized major surgical procedures in otolaryngology. Several studies have proposed the Clavien-Dindo classification (CDC) as a solution to classifying postoperative complications into 5 grades from less severe to severe. Yet more data on classifying larger patient populations undergoing major otolaryngolog ic surgery according to the CDC are needed. Predicting postoperative complications in clinical practice is often subject to generalized clinical scoring systems with uncertain predictive abilities for otolaryngologic surgery. Machine learning offers methods to predict postoperative complications based on data obtained prior to surgery. METHODS: We included all patients (N = 148) who underwent a total laryngectomy after diagnosis of squamous cell carcinoma at our institution. A univariate and multivariate logistic regression analysis of multiple complex risk factors was performed, and patients were grouped into severe postoperative complications (CDC ≥ 4) and less severe complications. Four different commonly used machine learning algorithms were trained on the dataset. The best model was selected to predict postoperative complications on the complete dataset. RESULTS: Univariate analysis showed that the most significant predictors for postoperative complications were t he Charlson Comorbidity Index (CCI) and whether reconstruction was performed intraoperatively. A multivariate analysis showed that the CCI and reconstruction remained significant. The commonly used AdaBoost algorithm achieved the highest area under the curve with 0.77 with high positive and negative predictive values in subsequent analysis. CONCLUSIONS: This study shows that postoperative complications can be classified according to the CDC with the CCI being a useful screening tool to predict patients at risk for postoperative complications. We provide evidence that could help identify single patients at risk for complications and customize treatment accordingly which could finally lead to a custom approach for every patient. We also suggest that there is no increase in complications with patients of higher age. PMID:34328819 | DOI:10.1177/01455613211029749 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Epiglottitis in Patients With Preexisting Autoimmune Diseases: A Nationwide Case-Control Study in Taiwan

xlomafota13 shared this article with you from Inoreader Epiglottitis in Patients With Preexisting Autoimmune Diseases: A Nationwide Case-Control Study in Taiwan Via ear nose throat Ear Nose Throat J. 2021 Jul 30:1455613211033689. doi: 10.1177/01455613211033689. Online ahead of print. ABSTRACT OBJECTIVES: The role of autoimmune diseases on the risk for acute epiglottitis remains uncertain. This study aimed to delineate the association between epiglottitis and autoimmune diseases using population database. METHODS: A population-based retrospective study was conducted to analyze claims data from Taiwan National Health Insurance Research Database col lected over January, 2000, to December, 2013. RESULTS: In total, 2339 patients with epiglottitis were matched with 9356 controls without epiglottitis by sex, age, socioeconomic status, and urbanization level. The correlation between autoimmune diseases and epiglottitis was analyzed by multivariate logistic regression. Compared with controls, patients with epiglottitis were much more likely to have preexisting Sjögren syndrome (adjusted odds ratio [aOR]: 2.37; 95% CI: 1.14-4.91; P = .021). In addition, polyautoimmunity was associated with increased risk of epiglottitis (aOR: 2.08; 95% CI: 1.14-3.80; P = .018), particularly in those aged >50 years (aOR: 2.61; 95% CI: 1.21-5.66; P = .015). CONCLUSIONS: Among autoimmune diseases, we verify the association between epiglottitis and Sjögren syndrome in Taiwan. Furthermore, we present the novel discovery that patients with epiglottitis have an increased risk of polyautoimmunity, particularly those aged >50 years. PMID:34328820 | DOI:10.1177/01455613211033689 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.