Πέμπτη 11 Νοεμβρίου 2021

Fine Needle Aspiration Cytology Implementation and Malignancy Rates in Children and Adolescents Based on Japanese Guidelines: The Fukushima Health Management Survey

xlomafota13 shared this article with you from Inoreader

showCoverImage?journalCode=

Thyroid, Volume 31, Issue 11, Page 1683-1692, November 2021.
View on the web

XB130 Deficiency Causes Congenital Hypothyroidism in Mice due to Disorganized Apical Membrane Structure and Function of Thyrocytes

xlomafota13 shared this article with you from Inoreader

showCoverImage?journalCode=

Thyroid, Volume 31, Issue 11, Page 1650-1661, November 2021.
View on the web

Two novel mutations of the γ‐secretase genes in Chinese acne inversa (hidradenitis suppurativa)

xlomafota13 shared this article with you from Inoreader
View on the web

MicroRNA profiling of psoriatic skin identifies 11 miRNAs associated with disease severity

xlomafota13 shared this article with you from Inoreader

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as central regulators of gene expression and powerful biomarkers of disease. Much is yet unknown about their role in psoriasis pathology. To globally characterize the miRNAome of psoriatic skin, skin biopsies were collected from psoriatic cases (n = 75) and non-psoriatic controls (n = 46) and RNA sequenced. Count data was meta-analyzed with a previously published dataset (cases, n = 24, controls, n = 20), increasing the number of psoriatic cases four-fold from previously published studies. Differential gene expression analyses were performed comparing lesional psoriatic (PP), non-lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell-specific analyses were performed. Across all contrasts, we identified 439 significantly differentially expressed miRNAs (DEMs), of which 85 were novel for psoriasis and 11 were related to disease severity. Meta-analyses identified 20 DEMs between PN and NN, suggesting an inherent change in the constitution of all skin in psoriasis. By integrating the miRNA transcriptome with mRNA target interactions, we identified several functionally enriched terms, including 'thyroid hormone signaling', 'insulin resistance' and various infectious diseases. Cell-specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells. This study provides the most comprehensive overview of the miRNAome in psoriatic skin to date and identifies a miRNA signature related to psoriasis severity. Our results may represent molecular links between psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify biomarkers and treatment targets.

View on the web

Oral supplementation of inorganic pyrophosphate in pseudoxanthoma elasticum

xlomafota13 shared this article with you from Inoreader

ABSTRACT

Pseudoxanthoma elasticum (PXE; OMIM 264800) is a rare heritable multisystem disorder, characterized by ectopic mineralization affecting elastic fibers in the skin, eyes, and the cardiovascular system. Skin findings often lead to early diagnosis of PXE, but currently no specific treatment exists to counteract the progression of symptoms.

PXE belongs to a group of Mendelian calcification disorders linked to pyrophosphate metabolism, which also includes generalized arterial calcification of infancy (GACI), and arterial calcification due to CD73 deficiency (ACDC). Inactivating mutations in ABCC6, ENPP1 and NT5E are the genetic cause of these diseases, respectively, and all of them result in reduced inorganic pyrophosphate (PPi) concentration in the circulation. Although PPi is a strong inhibitor of ectopic calcification, oral supplementation therapy was initially not considered because of its low bioavailability. Our earlier work however demonstrated that orally administered pyrophosphate inhibits ectopic calcification in the animal models of PXE and GACI, and that orally given Na4P2O7 is absorbed in humans.

Here we report that gelatin encapsulated Na2H2P2O7 has similar absorption properties in healthy volunteers and people affected by PXE. The sodium-free K2H2P2O7 form resulted in similar uptake in healthy volunteers, and inhibited calcification in Abcc6-/- mice as effectively as its sodium counterpart. Novel pyrophosphate compounds showing higher bioavailability in mice were also identified. Our results provide an important step toward testing oral PPi in clinical trials in PXE, or potentially any condition accompanied by ectopic calcification including diabetes, chronic kidney disease or ageing.

View on the web

IFN‐γ‐induced PD‐L1 expression on human melanocytes is impaired in vitiligo

xlomafota13 shared this article with you from Inoreader

ABSTRACT

Mounting evidence shows that the PD-1/PD-L1 axis is involved in tumor immune evasion. This is demonstrated by anti-PD-1 antibodies that can reverse tumor-associated PD-L1 to functionally suppress anti-tumor T cell responses. Since type I and II interferons are key regulators of PD-L1 expression in melanoma cells and IFN-γ-producing CD8+ T cells and IFN-α-producing dendritic cells are abundant in vitiligo skin, we aimed to study the role of PD-1/PD-L1 signaling in melanocyte destruction in vitiligo. Moreover, impaired PD-1/PD-L1 function is observed in a variety of autoimmune diseases. It is therefore hypothesized that manipulating PD-1/PD-L1 signaling might have therapeutic potential in vitiligo.

PD-1+ T cells were abundantly present in situ in perilesional vitiligo skin, but expression of PD-L1 was limited and confined exclusively to dermal T cells. More specifically, neither melanocytes nor other epidermal skin cells expressed PD-L1. Exposure to IFN-γ, but also type I interferons, increased PD-L1 expression in primary melanocytes and fibroblasts, derived from healthy donors. Primary human keratinocytes only showed increased PD-L1 expression upon stimulation with IFN-γ. Most interestingly, melanocytes derived from non-lesional vitiligo skin showed no PD-L1 upregulation upon IFN-γ exposure, while other skin cells displayed significant PD-L1 expression after exposure. In a vitiligo skin explant model, incubation of non-lesional vitiligo skin with activated (IFN-γ-producing) T cells from vitiligo lesions was previously described to induce melanocyte apoptosis. Although PD-L1 expression was induced in epidermal cells in these explants, this induction was completely absent in melanocytes.

The lack of PD-L1 upregulation by melanocytes in the presence of IFN-γ-producing T cells shows that melanocytes lack protection against T cell attack during vitiligo pathogenesis. Manipulating PD-1/PD-L1 signaling may therefore be a therapeutic option for vitiligo patients.

View on the web

Τετάρτη 10 Νοεμβρίου 2021

Overview of sialylation status in human nervous and skeletal muscle tissues during aging

xlomafota13 shared this article with you from Inoreader
Via histochem

pubmed-meta-image.png

Acta Histochem. 2021 Nov 6;123(8):151813. doi: 10.1016/j.acthis.2021.151813. Online ahead of print.

ABSTRACT

Sialic acids (Sias) are a large and heterogeneous family of electronegatively charged nine-carbon monosaccharides containing a carboxylic acid and are mostly found as terminal residues in glycans of glycoproteins and glycolipids such as gangliosides. They are linked to galactose or N-acetylgalactosamine via α2,3 or α2,6 linkage, or to other Sias via α2,8 or more ra rely α2,9 linkage, resulting in mono, oligo and polymeric forms. Given their characteristics, Sias play a crucial role in a multitude of human tissue biological processes in physiological and pathological conditions, ranging from development and growth to adult life until aging. Here, we review the sialylation status in human adult life focusing on the nervous and skeletal muscle tissues, which both display significant structural and functional changes during aging, strongly impacting on the whole human body and, therefore, on the quality of life. In particular, this review highlights the fundamental roles played by different types of glycoconjugates Sias in several cellular biological processes in the nervous and skeletal muscle tissues during adult life, also discussing how changes in Sia content during aging may contribute to the physiological decline of physical and nervous functions and to the development of age-related degenerative pathologies. Based on our current knowledge, further in-depth investigations could help to develop novel prophylactic strategies and therapeutic approaches that, by maintaining and/or restoring the correct sialylation status in the nervous and skeletal muscle tissues, could contribute to aging slowing and the prevention of age-related pathologies.

PMID:34753032 | DOI:10.1016/j.acthis.2021.151813

View on the web