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Yixing Yu, Ximing Wang, Cen Shi, Su Hu, Hui Zhu, Chunhong Hu
OBJECTIVE: The aim of this study was to explore the value of spectral computed tomography (CT) imaging in differentiating lung cancer from inflammatory myofibroblastic tumor (IMT). METHODS: One hundred twelve patients with 96 lung cancers and 16 IMTs underwent spectral CT during arterial phase (AP) and venous phase (VP). The normalized iodine concentration in AP (NICAP) and VP (NICVP), slope of spectral Hounsfield unit curve in AP (λAP) and VP (λVP), and normalized iodine concentration difference between AP and VP (ICD) were calculated...
February 11, 2019: Journal of Computer Assisted Tomography
Ivonne Loeffler
Interstitial fibrosis is a typical feature of end-stage renal diseases, regardless of the initial cause of kidney injury. Epithelial-to-mesenchymal transition (EMT) is a mechanism that is thought to play a role in generating the interstitial matrix-producing myofibroblasts and is prominently induced by the transforming growth factor-β 1 (TGF-β1). TGF-β1 signals through a variety of Smad and non-Smad signaling pathways, including the mitogen-activated protein kinase (MAPK) pathways. In a study published in a recent issue of Clinical Science (Clin...
February 14, 2019: Clinical Science (1979-)
Ruth Saunders, Himanshu Kaul, Rachid Berair, Sherif Gonem, Amisha Singapuri, Amanda J Sutcliffe, Latifa Chachi, Michael S Biddle, Davinder Kaur, Michelle Bourne, Ian D Pavord, Andrew J Wardlaw, Salman H Siddiqui, Richard A Kay, Bindi S Brook, Rod H Smallwood, Christopher E Brightling
Increased airway smooth muscle mass, a feature of airway remodeling in asthma, is the strongest predictor of airflow limitation and contributes to asthma-associated morbidity and mortality. No current drug therapy for asthma is known to affect airway smooth muscle mass. Although there is increasing evidence that prostaglandin D2 type 2 receptor (DP2 ) is expressed in airway structural and inflammatory cells, few studies have addressed the expression and function of DP2 in airway smooth muscle cells. We report that the DP2 antagonist fevipiprant reduced airway smooth muscle mass in bronchial biopsies from patients with asthma who had participated in a previous randomized placebo-controlled trial...
February 13, 2019: Science Translational Medicine
Christian Salib, Morris Edelman, Joshua Lilly, John E Fantasia, Aaron E Yancoskie
Cranial fasciitis (CF) is an uncommon benign myofibroblastic proliferation involving the soft and hard tissues of the cranium. It typically occurs in the pediatric population with a male predilection (male-to-female ratio 1.5:1). The clinical presentation is usually a rapidly expanding, painless nodule. Bone erosion may be appreciated radiographically. Histopathologic sections of CF show plump, fibroblast-like cells with pale, oval shaped nuclei and prominent nucleoli in a fibrous or myxoid background. Growth is self-limited and surgical excision is considered curative...
February 13, 2019: Head and Neck Pathology
Jonathan C P Roos, Rachna Murthy
BACKGROUND: Rapamycin (alternatively known as sirolimus) is a macrolide immunosuppressant commonly used for organ transplantation. It acts both on lymphocytes through the mechanistic target of rapamycin (mTOR) pathway to reduce their sensitivity to interleukin-2 (IL-2) and, importantly, also has anti-fibrotic properties by acting on myofibroblasts. The latter have been implicated in the pathogenesis of thyroid eye disease (TED). AIM: To describe successful treatment and reversal of extraocular muscle fibrosis in TED with sirolimus...
February 12, 2019: Eye
Ji Hyun Kim, Chang Ho Lee, Seong-Wook Lee
The mechanism by which hepatitis C virus (HCV) causes fibrosis and other chronic liver diseases remains poorly understood. Previously, we observed that HCV infection induces microRNA-192 (miR-192) expression, which in turn upregulates transforming growth factor β1 (TGF-β1) in hepatocytes. In this study, we aimed to determine the roles and mechanisms of HCV-induced miR-192 expression during chronic liver injury and fibrosis and to identify potential target of the liver disease. Noticeably, miR-192 is secreted and transmitted through exosomes from HCV-replicating hepatocytes into hepatic stellate cells (HSCs)...
January 18, 2019: Molecular Therapy. Nucleic Acids
Quang T Nguyen, Mohamed Jalloul Nsaibia, Martin G Sirois, Angelino Calderone, Jean-Claude Tardif, Yan Fen Shi, Matthieu Ruiz, Caroline Daneault, Lyne Gagnon, Brigitte Grouix, Pierre Laurin, Jocelyn Dupuis
Aims: Heart failure with reduced ejection fraction (HFrEF) causes lung remodelling with myofibroblasts proliferation and fibrosis leading to a restrictive lung syndrome with pulmonary hypertension (PH) and right ventricular (RV) dysfunction. PBI-4050 is a first-in-class anti-fibrotic, anti-inflammatory and anti-proliferative compound. The present study evaluated the therapeutic impact of PBI-4050 on PH in an HFrEF model. Methods and Results: HFrEF was induced after myocardial infarction (MI) in rats...
February 7, 2019: Cardiovascular Research
Dezhi Zheng, Yong Zhang, Yonghe Hu, Jing Guan, Lianbin Xu, Wenjing Xiao, Qinyue Zhong, Chao Ren, Jinfeng Lu, Jiali Liang, Jun Hou
Diabetic cardiomyopathy (DCM) - ventricular dysfunction in the absence of underlying heart disease - is a common complication of diabetes and a leading cause of mortality associated with the disease. In DCM, cardiac fibrosis is the main cause of heart failure (HF). Although it is well-established that the transforming growth factor-beta (TGF-β) signaling pathway plays a part in inducing cardiac fibrosis in DCM, details of the molecular mechanism involved remain elusive. Therefore, it is crucial to study the gene regulation of key signaling effectors in DCM-associated cardiac fibrosis...
February 12, 2019: FEBS Journal
Chen Sai, Jiang Yunhan, Jian Zhao, Zhu Yu, Zhu Yun, Cao Zhezhe, Tang Fuqin, Ma Ruiyan, Xiao Yingbin
Atrial fibrillation has caused severe burden for people worldwide. Differentiation of fibroblasts into myofibroblasts, and consequent progress in atrial structural remodeling have been considered the basis for persistent atrial fibrillation, yet little is known about the molecular mechanisms underlying the process. Here, we show that cyclin-dependent kinase 1 (CDK1) is activated in atrial fibroblasts from patients with atrial fibrillation (AFPAF) and in platelet derived growth factor BB (PDGF-BB)-treated atrial fibroblasts from patients with sinus rhythm (AFPSR)...
February 8, 2019: International Heart Journal
Yasunobu Ishikawa, Sorin Fedeles, Arnaud Marlier, Chao Zhang, Anna-Rachel Gallagher, Ann-Hwee Lee, Stefan Somlo
BACKGROUND: SEC63 encodes a resident protein in the endoplasmic reticulum membrane that, when mutated, causes human autosomal dominant polycystic liver disease. Selective inactivation of Sec63 in all distal nephron segments in embryonic mouse kidney results in polycystin-1-mediated polycystic kidney disease (PKD). It also activates the Ire1 α -Xbp1 branch of the unfolded protein response, producing Xbp1s, the active transcription factor promoting expression of specific genes to alleviate endoplasmic reticulum stress...
February 11, 2019: Journal of the American Society of Nephrology: JASN
Shabnam Zarei, Fadi W Abdul-Karim, Dana M Chase, Caroline Astbury, Maria Luisa C Policarpio-Nicolas
Inflammatory myofibroblastic tumors (IMTs) are spindle cell neoplasms of intermediate (borderline) biologic potential with tendency for local recurrence but low risk of metastasis. They affect children more than adults. The most common sites of involvement are the lung, soft tissue, peritoneum, bladder, and less commonly the gynecologic tract. IMTs are characterized by spindle to epithelioid cells with myofibroblastic differentiation, some degree of smooth muscle differentiation, myxoid stroma and usually associated with brisk lymphoplasmacytic infiltrates...
February 7, 2019: International Journal of Gynecological Pathology
Hironobu Nishina, Chisa Katou-Ichikawa, Mizuki Kuramochi, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
A3, generated as a monoclonal antibody against rat malignant fibrous histiocytoma (MFH)-derived cloned cells, recognizes somatic stem cells (bone-marrow/hair follicle stem cells). We investigated the distribution of cells immunoreactive to A3 in the developing rat intestine (particularly, the colon), focusing on the ontogenic kinetics of A3-positive cells. In the rat intestine, A3 labeled spindle-shaped stromal cells localized in the submucosa and labeled endothelial cells of capillaries in the lamina propria forming villi in the early development stage...
January 2019: Journal of Toxicologic Pathology
Annalucia Virdi, Carlotta Baraldi, Alessia Barisani, Barbara Corti, Francesco Savoia, Annalisa Patrizi, Iria Neri
Plaque-like myofibroblastic tumor is a rare and benign pediatric soft tissue tumor. It presents as a slowly growing plaque reaching several centimeters in diameter, made up of multiple nodules. The clinical and histological features of this benign entity are similar to other fibrohistiocytic or myofibroblastic tumors occuring in childhood, so the diagnosis can be difficult. The correlation between clinical data, histopathology and immunohistochemistry is necessary for the correct diagnosis. This article is protected by copyright...
February 9, 2019: Journal of Cutaneous Pathology
Christian F Guerrero-Juarez, Priya H Dedhia, Suoqin Jin, Rolando Ruiz-Vega, Dennis Ma, Yuchen Liu, Kosuke Yamaga, Olga Shestova, Denise L Gay, Zaixin Yang, Kai Kessenbrock, Qing Nie, Warren S Pear, George Cotsarelis, Maksim V Plikus
During wound healing in adult mouse skin, hair follicles and then adipocytes regenerate. Adipocytes regenerate from myofibroblasts, a specialized contractile wound fibroblast. Here we study wound fibroblast diversity using single-cell RNA-sequencing. On analysis, wound fibroblasts group into twelve clusters. Pseudotime and RNA velocity analyses reveal that some clusters likely represent consecutive differentiation states toward a contractile phenotype, while others appear to represent distinct fibroblast lineages...
February 8, 2019: Nature Communications
Jianhua Ling, Paul J Chiao
In this issue of Cancer Discovery , Biffi and colleagues report that IL1 signaling cascades resulted in JAK/STAT activation and promoted an inflammatory cancer-associated fibroblast (iCAF) state, which contributed to the establishment of distinct fibroblast niches in the pancreatic ductal adenocarcinoma (PDAC) microenvironment to support the growth of PDAC cells. Furthermore, the investigators demonstrated that TGFβ signaling inhibited IL1R1 expression, antagonized IL1α responses, and promoted differentiation of CAFs into myofibroblasts; thus, IL1α signaling is an important therapeutic target for both PDAC cells and the iCAFs in the tumor microenvironment...
February 2019: Cancer Discovery
Xiaoke Wang, Yang Chen, Xiujuan Wu, Hongliang Zhang
Inflammatory myofibroblastic tumor (IMT) is an indolent tumor mainly affecting children and young adults. As a rare mesenchymal tumor with unknown etiology and pathogenesis, IMT has a predilection for lung and abdominopelvic region. Previous literature featuring on IMT in the central nervous system (IMT-CNS) was rare. The clinical symptoms and radiological features of IMT-CNS are not specific, and therefore the diagnosis is predominately based on the histopathological and immunohistochemical analysis of the specimen...
February 5, 2019: World Neurosurgery
Xingya Zhu, Hongying Gan-Schreier, Ann-Christin Otto, Yuting Cheng, Simone Staffer, Sabine Tuma-Kellner, Alexandra Ganzha, Gerhard Liebisch, Walee Chamulitrat
Group VIA calcium-independent phospholipase A2 (iPla2β) is among modifier genes of non-alcoholic fatty liver disease which leads to non-alcoholic steatohepatitis (NASH). Consistently, iPla2β deletion protects hepatic steatosis and obesity in genetic ob/ob and obese mice chronically fed with high-fat diet by replenishing the loss of hepatic phospholipids (PL). As mouse feeding with methionine- and choline-deficient (MCD) diet is a model of lean NASH, we tested whether iPla2β-null mice could still be protected since PL syntheses are disturbed...
February 5, 2019: Biochimica et biophysica acta. Molecular and cell biology of lipids
Giuseppe Piarulli, Florian Puls, Bo Wängberg, Henrik Fagman, Magnus Hansson, Jenny Nilsson, Elsa Arbajian, Fredrik Mertens
Inflammatory myofibroblastic tumour (IMT) is a soft tissue tumour primarily affecting children and young adults. Approximately 50% of IMTs have gene fusions involving the receptor tyrosine kinase (RTK)-encoding ALK gene, providing a molecular rationale for treating IMT patients with unresectable tumours with tyrosine kinase inhibitors (TKI). However, a subset of IMT instead displays fusions affecting other RTK-encoding genes, so far including NTRK3, PDGFRB, and ROS1. Also IMTs with variant RTK fusions may respond well to TKI treatment, but can be difficult to identify as they are negative for ALK staining at immunohistochemistry, the standard method for detection of ALK rearrangements...
February 8, 2019: Histopathology
Takeshi Masuda, Taku Nakashima, Masashi Namba, Kakuhiro Yamaguchi, Shinjiro Sakamoto, Yasushi Horimasu, Shintaro Miyamoto, Hiroshi Iwamoto, Kazunori Fujitaka, Yoshihiro Miyata, Hironobu Hamada, Morihito Okada, Noboru Hattori
Plasminogen activator inhibitor-1 (PAI-1) promotes pulmonary fibrosis through increasing myofibroblast (MF) characteristics, expressing alpha-smooth muscle actin (α-SMA) in fibroblasts. Fibroblasts in the tumour stroma are called cancer-associated fibroblasts (CAFs). Some CAFs have MF characteristics and substantially promote tumour progression and chemotherapy resistance. This study determined whether inhibition of PAI-1 suppressed MF characteristics of CAFs and limited chemotherapy resistance in lung cancer...
February 7, 2019: Journal of Cellular and Molecular Medicine
Xingang Zhou, Peng Wang, Zhiyuan Ma, Man Li, Xiaoying Teng, Lei Sun, Gang Wan, Yang Li, Limei Guo, Honggang Liu
Nonalcoholic steatohepatitis (NASH) has the potential to progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Upregulation of sonic hedgehog (Shh) has been documented in development of NASH through sustained cell stress. At the same time, transforming growth factor-β1 (TGF-β1), which is a central element in fibrogenic reactions in various diseases and sites, has been reported to be associated with hepatic inflammation and fibrotic reaction. To explore crosstalk between Shh and TGF-β1 in the development and progression of NASH, we investigated the expression of both these proteins in 135 human specimens of NASH, 35 fatty liver specimens, 35 specimens of alcoholic steatohepatitis with immunohistochemistry...
February 1, 2019: Applied Immunohistochemistry & Molecular Morphology: AIMM
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