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Molecular pathology

Sowmya Mekala, Subbarao V Tullimilli, Ramasatyaveni Geesala, Kanakaraju Manupati, Neha R Dhoke, Amitava Das
Apoptotic hepatocytes release factors that activate Hepatic Stellate Cells (HSCs) thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride or thioacetamide. Hepatotoxicant-induced diseased hepatic tissue histology correlated with a differential expression of fibrosis-related genes. Marked increase in co-staining of TGFRIIβ-Desmin or α-SMA-PDGFRβ, markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V-Cytokeratin expressing hepatocytes...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
Jelena Krstic, Markus Galhuber, Tim J Schulz, Michael Schupp, Andreas Prokesch
Lifestyle-related disorders, such as the metabolic syndrome, have become a primary risk factor for the development of liver pathologies that can progress from hepatic steatosis, hepatic insulin resistance, steatohepatitis, fibrosis and cirrhosis, to the most severe condition of hepatocellular carcinoma (HCC). While the prevalence of liver pathologies is steadily increasing in modern societies, there are currently no approved drugs other than chemotherapeutic intervention in late stage HCC. Hence, there is a pressing need to identify and investigate causative molecular pathways that can yield new therapeutic avenues...
March 20, 2018: International Journal of Molecular Sciences
Bayardo Perez-Ordoñez
Primary neuroendocrine carcinomas (NECs) of the larynx and head and neck are an uncommon and heterogeneous group of neoplasms categorized by the 2017 WHO Classification of Head and Neck Tumors as: (a) well-differentiated (WD-NEC), (b) moderately-differentiated (MD-NEC), and (c) poorly-differentiated (PD-NEC) with small cell and large cell types. The classification incorporates elements of differentiation and grading and closely correlates to the 5-year disease specific survival of 100, 52.8, 19.3 and 15.3% for each diagnostic category...
March 20, 2018: Head and Neck Pathology
Diane Penndorf, Otto W Witte, Alexandra Kretz
The pathophysiology of amyotrophic lateral sclerosis (ALS) is particularly challenging due to the heterogeneity of its clinical presentation and the diversity of cellular, molecular and genetic peculiarities involved. Molecular insights unveiled several novel genetic factors to be inherent in both familial and sporadic disease entities, whose characterizations in terms of phenotype prediction, pathophysiological impact and putative prognostic value are a topic of current researches. However, apart from genetically well-defined high-confidence and other susceptibility loci, the role of DNA damage and repair strategies of the genome as a whole, either elicited as a direct consequence of the underlying genetic mutation or seen as an autonomous parameter, in the initiation and progression of ALS, and the different cues involved in either process are still incompletely understood...
February 2018: Neural Regeneration Research
Rebecca D Chernock, Eric J Duncavage
Salivary neuroendocrine carcinomas are rare and the overwhelming majority is high-grade. The parotid gland is the most commonly involved site followed by the submandibular gland. Most arise de novo but rare examples occurring as a high-grade transformation of another type of salivary gland neoplasm exist. There is significant morphologic and immunophenotypic overlap with neuroendocrine carcinomas of other sites, especially the skin. Like cutaneous neuroendocrine (or Merkel cell) carcinomas, approximately three-fourths are cytokeratin 20 positive...
March 20, 2018: Head and Neck Pathology
Simone Scherrer, Patricia Landolt, Natasha Carroli, Roger Stephan
Mycobacterium avium subsp. hominissuis (MAH) is an important zoonotic pathogen with raising global health concerns. In humans, MAH is one of the most widespread non-tuberculous mycobacterial species responsible for lung disease. In animals, MAH is frequently isolated from pigs; however, it is also an opportunistic pathogen for other mammals including cattle. To elucidate the genetic diversity of MAH in cattle, a molecular characterization of isolates ( n  = 26) derived from lymph nodes was performed. Fourteen isolates originated from slaughtered cattle with visible altered lymph nodes at meat inspection, whereas 12 isolates were from lymph nodes without any gross pathological changes of healthy slaughtered cattle...
2018: Frontiers in Veterinary Science
Fei Yan, Yu Sun, Yang Mao, Meiying Wu, Zhiting Deng, Shuai Li, Xin Liu, Li Xue, Hairong Zheng
Cardiovascular diseases resulting from atherosclerosis have become a serious threat to human health. It is well-known that an ongoing inflammatory response is involved during atherosclerosis progression that ultimately results in the accumulation of lipids and formation of plaques. Monitoring the pathological changes during the inflammatory response will be of great significance for early diagnosis and therapeutic evaluation of atherosclerosis. Targeted contrast-enhanced ultrasonography has been shown to be a promising noninvasive imaging technique for evaluating the degree of atherosclerosis and may potentially be translated to clinical imaging in the future...
2018: Theranostics
Ilaria J Chicca, Michael R Milward, Iain Leslie C Chapple, Gareth Griffiths, Rod Benson, Thomas Dietrich, Paul R Cooper
Neutrophil extracellular traps (NETs) are DNA-based antimicrobial web-like structures whose release is predominantly mediated by reactive oxygen species (ROS); their purpose is to combat infections. However, unbalanced NET production and clearance is involved in tissue injury, circulation of auto-antibodies and development of several chronic diseases. Currently, there is lack of agreement regarding the high-throughput methods available for NET investigation. This study, therefore, aimed to develop and optimize a high-content analysis (HCA) approach, which can be applied for the assay of NET production and for the screening of compounds involved in the modulation of NET release...
2018: Frontiers in Immunology
Tao Wang, Zhong-Yi Qin, Liang-Zhi Wen, Yan Guo, Qin Liu, Zeng-Jie Lei, Wei Pan, Kai-Jun Liu, Xing-Wei Wang, Shu-Jie Lai, Wen-Jing Sun, Yan-Ling Wei, Lei Liu, Ling Guo, Yu-Qin Chen, Jun Wang, Hua-Liang Xiao, Xiu-Wu Bian, Dong-Feng Chen, Bin Wang
The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC)...
March 19, 2018: Cell Death and Differentiation
Lina Wang, Wenli Feng, Xiao Yang, Feifei Yang, Rong Wang, Qian Ren, Xiaofan Zhu, Guoguang Zheng
The ubiquitin-proteasome system (UPS) participates in both physiological and pathological processes through the posttranslational regulation of intracellular signal transduction pathways. F-box and WD-40 domain protein 11 (Fbxw11) is a component of the SCF (Skp1-Cul1-F-box) E3 ubiquitin ligase complex. Fbxw11 regulates various signal transduction pathways, and it may have pathological roles in tumorigenesis. However, the role of Fbxw11 in the development of leukemia and the underlying mechanisms remain largely unknown...
March 19, 2018: Cell Death & Disease
Justin O Szot, Hartmut Cuny, Gillian M Blue, David T Humphreys, Eddie Ip, Katrina Harrison, Gary F Sholler, Eleni Giannoulatou, Paul Leo, Emma L Duncan, Duncan B Sparrow, Joshua W K Ho, Robert M Graham, Nicholas Pachter, Gavin Chapman, David S Winlaw, Sally L Dunwoodie
BACKGROUND: Congenital heart disease (CHD)-structural abnormalities of the heart that arise during embryonic development-is the most common inborn malformation, affecting ≤1% of the population. However, currently, only a minority of cases can be explained by genetic abnormalities. The goal of this study was to identify disease-causal genetic variants in 30 families affected by CHD. METHODS: Whole-exome sequencing was performed with the DNA of multiple family members...
March 2018: Circ Genom Precis Med
Akihiko Kimura, Yuko Ishida, Machi Furuta, Mizuho Nosaka, Yumi Kuninaka, Akira Taruya, Naofumi Mukaida, Toshikazu Kondo
BACKGROUND: A clear understanding of the molecular mechanisms underlying hemodynamic stress-initiated cardiac hypertrophy is important for preventing heart failure. Interferon-γ (IFN-γ) has been suggested to play crucial roles in various diseases other than immunological disorders by modulating the expression of myriad genes. However, the involvement of IFN-γ in the pathogenesis of cardiac hypertrophy still remains unclear. METHODS AND RESULTS: In order to elucidate the roles of IFN-γ in pressure overload-induced cardiac pathology, we subjected Balb/c wild-type (WT) or IFN-γ-deficient ( Ifng -/- ) mice to transverse aortic constriction (TAC)...
March 19, 2018: Journal of the American Heart Association
Nuno Couto, Sergio Caja Galán, Joana Maia, Maria Carolina Strano Moraes, Bruno Costa-Silva
Oncologic diseases do not behave as isolated entities. Instead, they are based on complex systemic networks involving cell-cell communication between cancerous and healthy cells of the host, which may either facilitate or prevent cancer progression. In addition to cell-cell contacts, cells communicate through secreted factors in a process modulated by ligand concentration, receptor availability and synergy amongst several signaling circuits. Of these secreted factors, exosomes, 30 to 150 nm membrane vesicles of endocytic origin released by virtually all cells, have emerged as important cell-cell communication players both in physiological and pathological scenarios by being carriers of all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and performing intercellular transfer of components, locally and systemically...
March 16, 2018: Biochimie
Fazhao Li, Han Xiao, Zhiping Hu, Fangfang Zhou, Binbin Yang
HSPB8 is a member of ubiquitous small heat shock protein (sHSP) family, whose expression is induced in response to a wide variety of unfavorable physiological and environmental conditions. Investigation of HSPB8 structure indicated that HSPB8 belongs to the group of so-called intrinsically disordered proteins and possesses a highly flexible structure. Unlike most other sHSPs, HSPB8 tends to form small-molecular-mass oligomers and exhibits substrate-dependent chaperone activity. In cooperation with BAG3, the chaperone activity of HSPB8 was reported to be involved in the delivery of misfolded proteins to the autophagy machinery...
March 13, 2018: European Journal of Cell Biology
Julia R Schneider, Deborah R Shatzkes, Stephen C Scharf, Tristan M Tham, Kay O Kulason, François-Alexandre Buteau, Michela Del Prete, Shamik Chakraborty, Todd A Anderson, Saeed Asiry, Jean-Mathieu Beauregard, David J Langer, Peter D Costantino, John A Boockvar
BACKGROUND AND IMPORTANCE: Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors...
March 14, 2018: Operative Neurosurgery (Hagerstown, Md.)
Xin Zhao, Jing Wei, Xiaoxin Li, Haochang Yang, Pei Wang, Susheng Cao
Adequate lymph node evaluation is recommended for optimal staging in patients with malignant neoplasms including breast cancer. However, the role of negative lymph nodes (LNs) remains unclear in breast cancer according to N substage (N1, N2, and N3). In this study, for the first time, we analyzed the prognostic significance of negative LNs in breast cancer patients. A critical relationship was observed between negative LN count and survival, independent of patient characteristics and other related molecular variables including estrogen receptor (PR) status, progesterone receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, depth of tumor invasion and degree of differentiation...
2018: PloS One
Steven Quinn, Shwetha Srinivasan, Jesse Gordon, Wei He, Kermit L Carraway, Matthew A Coleman, Gabriela S Schlau-Cohen
The epidermal growth factor receptor (EGFR) is critical to normal cellular signaling pathways. Moreover, it has been implicated in a range of pathologies, including cancer. As a result, it is the primary target of many anti-cancer drugs. One limitation to the design and development of these drugs has been the lack of molecular-level information about the interactions and conformational dynamics of EGFR. To overcome this limitation, this work reports the development and characterization of functional fluorescently-labeled full-length EGFR in model membrane nanolipoprotein particles (NLPs) for in vitro fluorescence studies...
March 19, 2018: Biochemistry
Joseph Ochaba, Eva L Morozko, Jacqueline G O'Rourke, Leslie M Thompson
The accumulation of misfolded proteins is central to pathology in Huntington's disease (HD) and many other neurodegenerative disorders. Specifically, a key pathological feature of HD is the aberrant accumulation of mutant HTT (mHTT) protein into high molecular weight complexes and intracellular inclusion bodies composed of fragments and other proteins. Conventional methods to measure and understand the contributions of various forms of mHTT-containing aggregates include fluorescence microscopy, western blot analysis, and filter trap assays...
February 27, 2018: Journal of Visualized Experiments: JoVE
Polina Zjablovskaja, Petr Danek, Miroslava Kardosova, Meritxell Alberich-Jorda
Understanding of the hematopoietic stem and progenitor cell biology has important implications for regenerative medicine and the treatment of hematological pathologies. Despite the most relevant data that can be acquired using in vivo models or primary cultures, the low abundance of hematopoietic stem and progenitor cells considerably restricts the pool of suitable techniques for their investigation. Therefore, the use of cell lines allows sufficient production of biological material for the performance of screenings or assays that require large cell numbers...
February 21, 2018: Journal of Visualized Experiments: JoVE
Yi-Chen Lee, Shui-Chin Lu, Yu-Lin Hsieh
Patients with diabetes mellitus (DM) or those experiencing the neurotoxic effects of chemotherapeutic agents may develop sensation disorders due to degeneration and injury of small-diameter sensory neurons, referred to as small fiber neuropathy. Present animal models of small fiber neuropathy affect both large- and small-diameter sensory fibers and thus create a neuropathology too complex to properly assess the effects of injured small-diameter sensory fibers. Therefore, it is necessary to develop an experimental model of pure small fiber neuropathy to adequately examine these issues...
February 13, 2018: Journal of Visualized Experiments: JoVE
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