Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Thursday, January 14, 2021

Let-7a regulates EV secretion and mitochondrial oxidative phosphorylation by targeting SNAP23 in colorectal cancer

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MicroRNAs (miRNAs) are abundant in tumor-derived extracellular vesicles (EVs) and the functions of extracellular miRNA to recipient cells have been extensively studied with tumorigenesis. However, the role of ...
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Exploring determinants of hand hygiene compliance in LTCFs: a qualitative study using Flottorps’ integrated checklist of determinants of practice

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Elderly residents in long-term care facilities (LTCFs) are vulnerable to healthcare-associated infections. Although hand hygiene is a leading measure for preventing infection, the compliance of healthcare work...
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IGFBPs mediate IGF‐1's functions in retinal lamination and photoreceptor development during pluripotent stem cell differentiation to retinal organoids

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IGFBPs mediate IGF‐1's functions in retinal lamination and photoreceptor development during pluripotent stem cell differentiation to retinal organoids

In order to investigate the role of insulin growth factor binding proteins (IGFBPs) in retinal organoids, human embryonic stem cells (hESCs) were differentiated to retinal organoids using three different conditions: with IGF‐1 individually or in combination with NBI‐31772 (inhibitor of IGFBPs), and without IGF‐1. Retinal organoids were analyzed at three different time points: days 37, 90, and 120, showing an improvement in neural retinal organization and the appearance of different cell types over time. At day 120, IGF‐1 and NBI‐31722 + IGF‐1 treated organoids were characterized by the presence of all key cell types including photoreceptors precursors. Organoids cultured in the absence of IGF‐1 showed the least photoreceptor precursor generation and a predisposition toward the development of retinal ganglion cells. Together these data suggest that IGFBPs enable IGF‐1's role in retinal lamination and photoreceptor development in a stage‐specific manner.


Abstract

Development of the retina is regulated by growth factors such as insulin‐like growth factors 1 and 2 (IGF‐1/2), which coordinate proliferation, differentiation, and maturation of the neuroepithelial precursors cells. In the circulation, IGF‐1/2 are transported by the insulin growth factor binding proteins (IGFBPs) family members. IGFBPs can impact positively and negatively on IGF‐1, by making it available or sequestering IGF‐1 to or from its receptor. In this study, we investigated the expression of IGFBPs and their role in the generation of human retinal organoids from human pluripotent stem cells, showing a dynamic expression pattern suggestive of different IGFBPs being used in a stage‐specific manner to mediate IGF‐1 functions. Our data show that IGF‐1 addition to culture media facilitated the generation of retinal organoids displaying the typical laminated structure and photoreceptor maturation. The organoids cultured in the absence of IGF‐1, lacked the typic al laminated structure at the early stages of differentiation and contained significantly less photoreceptors and more retinal ganglion cells at the later stages of differentiation, confirming the positive effects of IGF‐1 on retinal lamination and photoreceptor development. The organoids cultured with the IGFBP inhibitor (NBI‐31772) and IGF‐1 showed lack of retinal lamination at the early stages of differentiation, an increased propensity to generate horizontal cells at mid‐stages of differentiation and reduced photoreceptor development at the later stages of differentiation. Together these data suggest that IGFBPs enable IGF‐1's role in retinal lamination and photoreceptor development in a stage‐specific manner.

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Effects of motion correction, sampling rate and parametric modelling in dynamic contrast enhanced MRI of the temporomandibular joint in children affected with juvenile idiopathic arthritis

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Publication date: April 2021

Source: Magnetic Resonance Imaging, Volume 77

Author(s): Lea Starck, Erling Andersen, Ondřej Macíček, Oskar Angenete, Thomas A. Augdal, Karen Rosendahl, Radovan Jiřík, Renate Grüner

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Interstitial granuloma after interferon‐gamma and narrow band UVB therapy in a patient with mycosis fungoides: immunological and histopathological considerations

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Abstract

In mycosis fungoides (MF), cutaneous granuloma formation is unusual. Furthermore, MF showing interstitial granuloma, a rare type, after combination therapy with interferon‐gamma (IFN‐γ) and narrow band UVB (nUVB) has not been previously reported. A 77‐year‐old man was referred to our hospital with a 2‐month history of erythroderma. Biopsied specimens revealed infiltration of atypical lymphocytes and eosinophils. A diagnosis of an erythrodermic variant of MF was made. He was treated with combination therapy of IFN‐γ and nUVB. After the therapy, papules newly appeared and a histopathological specimen revealed interstitial granuloma. There were several CXCR3‐positive cells around the granuloma. We speculated that the combination therapy made T‐helper 1 cells migrate to the cutaneous lesion and resulted in the granuloma formation. Furthermore, judging from the disappearance of elastic fibers around the interstitial granuloma, we considered that IFN‐γ may induce th e infiltration of histiocytes interstitially after damage of elastic fibers caused by nUVB therapy, and both IFN‐γ and nUVB may thus play an important role in the histogenesis. Not only histopathology but also immunological observations are needed to elucidate the mechanisms underlying the development of different types of granuloma in MF.

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Metastatic HPV‐Positive Oropharyngeal Carcinoma Mimicking Primary Cutaneous Sweat‐gland Carcinoma

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ABSTRACT

The practicing pathologist will see a wide variety of metastatic tumors to the skin, many of which are not easily identifiable as metastases through histopathologic exam or clinical history. Furthermore, primary origin of tumors thought to be metastatic may not be readily apparent through initial histopathologic exam alone. We report an unusual cutaneous metastasis of an HPV‐related oropharyngeal squamous cell carcinoma with histopathologic features that closely mimicked a primary cutaneous sweat gland carcinoma. Clinical correlation and tissue testing for human papilloma virus (HPV) allowed for the correct diagnosis. Testing for HPV may be considered for lesions of unknown primary with similar histopathology.

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Neferine suppresses autophagy‐induced inflammation, oxidative stress and adipocyte differentiation in Graves' orbitopathy

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Abstract

Previous studies in Graves' orbitopathy (GO) patient‐derived fibroblasts showed that inhibition of autophagy suppresses adipogenic differentiation. Autophagy activation is associated with inflammation, production of reactive oxygen species and fibrosis. Neferine is an alkaloid extracted from Nelumbo nucifera, which induces Nrf2 expression and inhibits autophagy. Here, we have elucidated the role of neferine on interleukin (IL)‐13‐induced autophagy using patient‐derived orbital fibroblasts as an in vitro model of GO. GO patient‐derived orbital fibroblasts were isolated and cultured to generate an in vitro model of GO. Autophagy was determined by Western blot detection of the markers such as Beclin‐1, Atg‐5 and LC3 and by immunofluorescence detection of autophagosome formation. Analysis of differentiation towards an adipogenic lineage was performed by Oil red O staining. The expression of inflammatory factors was detected by ELISA and semiquantitative RT‐PCR . Neferine inhibited autophagy in GO orbital fibroblasts, as indicated by the suppression of IL‐13‐induced autophagosome formation, overexpression of autophagy markers, increased LC3‐II/LC3‐I levels and finally down‐regulation of p62. Neferine suppressed IL‐13‐induced inflammation, ROS generation, fibrosis and adipogenic differentiation in GO patient‐derived orbital fibroblasts. The anti‐inflammatory, antioxidant and antiadipogenic effects of neferine were accompanied by the up‐regulation of Nrf2. These results indicated that orbital tissue remodelling and inflammation in GO may be mediated by autophagy, and neferine suppressed autophagy‐related inflammation and adipogenesis through a mechanism involving Nrf2.

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The role of SARS‐CoV‐2 target ACE2 in cardiovascular diseases

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Abstract

SARS‐CoV‐2, the virus responsible for the global coronavirus disease (COVID‐19) pandemic, attacks multiple organs of the human body by binding to angiotensin‐converting enzyme 2 (ACE2) to enter cells. More than 20 million people have already been infected by the virus. ACE2 is not only a functional receptor of COVID‐19 but also an important endogenous antagonist of the renin‐angiotensin system (RAS). A large number of studies have shown that ACE2 can reverse myocardial injury in various cardiovascular diseases (CVDs) as well as is exert anti‐inflammatory, antioxidant, anti‐apoptotic and anticardiomyocyte fibrosis effects by regulating transforming growth factor beta, mitogen‐activated protein kinases, calcium ions in cells and other major pathways. The ACE2/angiotensin‐(1‐7)/Mas receptor axis plays a decisive role in the cardiovascular system to combat the negative effects of the ACE/angiotensin II/angiotensin II type 1 receptor axis. However, the underlying mechanism of ACE2 in cardiac protection remains unclear. Some approaches for enhancing ACE2 expression in CVDs have been suggested, which may provide targets for the development of novel clinical therapies. In this review, we aimed to identify and summarize the role of ACE2 in CVDs.

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Study Suggests a Link between Stress and Cancer Coming Back

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Cancer cells that are leftover after treatment can go into a "dormant" state for years. A new study in mice suggests that stress hormones may trigger a chain reaction that wakes up dormant cancer cells, causing tumors to form again.
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Predicting pathological complete response (pCR) after stereotactic ablative radiation therapy (SABR) of lung cancer using quantitative dynamic [18F]FDG PET and CT perfusion: a prospective exploratory clinical study

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Stereotactic ablative radiation therapy (SABR) is effective in treating inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. This prospective study...
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A Prognostic Gene Signature for Predicting Survival Outcome in Diffuse Large B-Cell Lymphoma

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Publication date: Available online 13 January 2021

Source: Cancer Genetics

Author(s): Santosh Khanal, Todd Bradley

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Promoter hypermethylation regulates vitamin D receptor (VDR) expression in colorectal cancer-A study from Kashmir valley

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Publication date: Available online 13 January 2021

Source: Cancer Genetics

Author(s): Falaque ul Afshan, Akbar Masood, Bushra Nissar, Nisar Ahmad Chowdri, Niyaz Ahmad Naykoo, Misbah Majid, Bashir Ahmad Ganai

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