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Cellular pathology

Akihisa Kato, Itaru Naitoh, Hiroyuki Kato, Kazuki Hayashi, Katsuyuki Miyabe, Michihiro Yoshida, Yasuki Hori, Makoto Natsume, Naruomi Jinno, Takeshi Yanagita, Shuji Takiguchi, Satoru Takahashi, Takashi Joh
Endoscopic transpapillary brush cytology and forceps biopsy during endoscopic retrograde cholangiopancreatology are generally used to obtain pathological evidence of biliary strictures. Recently, the new endoscopic scraper Trefle® has been reported and demonstrated high cancer detectability in malignant biliary strictures. This device is used to scrape the stricture over the guidewire, and, in the original method, the tissue and/or cell samples obtained are subjected to histological and/or cytological analysis separately...
March 15, 2018: World Journal of Gastrointestinal Oncology
Oliver Edenharter, Stephan Schneuwly, Juan A Navarro
Friedreich's ataxia (FRDA) is the most important recessive ataxia in the Caucasian population. It is caused by a deficit of the mitochondrial protein frataxin. Despite its pivotal effect on biosynthesis of iron-sulfur clusters and mitochondrial energy production, little is known about the influence of frataxin depletion on homeostasis of the cellular mitochondrial network. We have carried out a forward genetic screen to analyze genetic interactions between genes controlling mitochondrial homeostasis and Drosophila frataxin...
2018: Frontiers in Molecular Neuroscience
Dezhi Li, Yu Zhou, Yanhui Liu, Ye Lin, Min Yu, Xin Lu, Bowen Huang, Zhonghai Sun, Zhixiang Jian, Baohua Hou
Background: Liver kinase B1 (LKB1) is a key regulatory protein of cellular metabolism, proliferation, and polarity. The present study aimed to characterize the expression pattern of LKB1 in pancreatic neuroendocrine tumors (pNETs) and evaluate the relationship between LKB1 expression and prognosis in pNETs. Patients and methods: We retrospectively analyzed the pathologic and clinical data of 71 pNET patients who underwent curative surgical resection in Guangdong General Hospital...
2018: OncoTargets and Therapy
Styliani Vakrou, Ryuya Fukunaga, D Brian Foster, Lars Sorensen, Yamin Liu, Yufan Guan, Kirubel Woldemichael, Roberto Pineda-Reyes, Ting Liu, Jill C Tardiff, Leslie A Leinwand, Carlo G Tocchetti, Theodore P Abraham, Brian O'Rourke, Miguel A Aon, M Roselle Abraham
Hypertrophic cardiomyopathy (HCM) stems from mutations in sarcomeric proteins that elicit distinct biophysical sequelae, which in turn may yield radically different intracellular signaling and molecular pathologic profiles. These signaling events remain largely unaddressed by clinical trials that have selected patients based on clinical HCM diagnosis, irrespective of genotype. In this study, we determined how two mouse models of HCM differ, with respect to cellular/mitochondrial function and molecular biosignatures, at an early stage of disease...
March 22, 2018: JCI Insight
Denise C Hsu, Piyanate Sunyakumthorn, Matthew Wegner, Alexandra Schuetz, Decha Silsorn, Jacob D Estes, Claire Deleage, Khamis Tomusange, Samir K Lakhashe, Ruth M Ruprecht, Eric Lombardini, Rawiwan Im-Erbsin, Yanin Kuncharin, Yuwadee Phuang-Ngern, Dutsadee Inthawong, Weerawan Chuenarom, Robin Burke, Merlin L Robb, Lishomwa C Ndhlovu, Jintanat Ananworanich, Victor Valcour, Robert J O'Connell, Serena Spudich, Nelson L Michael, Sandhya Vasan
Studies utilizing highly pathogenic simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) have largely focused on the immunopathology of the central nervous system (CNS) during end-stage neuro AIDS and SIV encephalitis. However, this may not model pathophysiology in earlier stages of infection. In this non-accelerated SHIV model, plasma SHIV RNA levels and peripheral blood and colonic CD4 T+ cell counts mirrored early HIV infection in humans. At 12 weeks post infection, cerebrospinal fluid (CSF) detection of SHIV RNA and elevations in IP-10 and MCP-1 reflected a discrete neurovirologic process...
March 21, 2018: Journal of Virology
Leigh Zerboni, Phillip Sung, Gordon Lee, Ann Arvin
Varicella-zoster virus (VZV) is the skin-tropic human alphaherpesvirus responsible for both varicella and herpes zoster. Varicella and herpes zoster skin lesions have similar morphology but herpes zoster occurs disproportionally in older individuals and is often associated with a more extensive local rash and severe zoster-related neuralgia. We hypothesized that skin aging could also influence the outcome of the anterograde axonal transport of VZV to skin. We utilized human skin xenografts maintained in immunodeficient (SCID) mice to study VZV-induced skin pathology in vivo in fetal and adult skin xenografts...
March 21, 2018: Journal of Virology
Evelia Y Salinas, Jerry C Hu, Kyriacos A Athanasiou
The use of tissue-engineered articular cartilage (AC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in-vivo use have yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC...
March 21, 2018: Tissue Engineering. Part B, Reviews
Masanori Takabayashi, Hassaan Majeed, Andre Kajdacsy-Balla, Gabriel Popescu
Tissue refractive index provides important information about morphology at the nanoscale. Since the malignant transformation involves both intra- and inter-cellular changes in the refractive index map, the tissue disorder measurement can be used to extract important diagnosis information. Quantitative phase imaging (QPI) provides a practical means of extracting this information as it maps the optical path-length difference (OPD) across a tissue sample with sub-wavelength sensitivity. In this work, we employ QPI to compare the tissue disorder strength between benign and malignant breast tissue histology samples...
2018: PloS One
Christiana Leimena, Hongyu Qiu
Hypertension is a complex, multifactorial disease that involves the coexistence of multiple risk factors, environmental factors and physiological systems. The complexities extend to the treatment and management of hypertension, which are still the pursuit of many researchers. In the last two decades, various genes have emerged as possible biomarkers and have become the target for investigations of specialized drug design based on its risk factors and the primary cause. Owing to the growing technology of microarrays and next-generation sequencing, the non-protein-coding RNAs (ncRNAs) have increasingly gained attention, and their status of redundancy has flipped to importance in normal cellular processes, as well as in disease progression...
March 21, 2018: International Journal of Molecular Sciences
Tomoko Hasegawa, Hanako Ohashi Ikeda, Sachiko Iwai, Yuki Muraoka, Tatsuaki Tsuruyama, Keiko Okamoto-Furuta, Haruyasu Kohda, Akira Kakizuka, Nagahisa Yoshimura
Retinal neuronal cell death underlies many incurable eye diseases such as retinitis pigmentosa (RP) and glaucoma, and causes adult blindness. We have shown that maintenance of ATP levels via inhibiting ATP consumption is a promising strategy for preventing neuronal cell death. Here, we show that branched chain amino acids (BCAAs) are able to increase ATP production by enhancing glycolysis. In cell culture, supplementation of the culture media with BCAAs, but not glucose alone, enhanced cellular ATP levels, which was canceled by a glycolysis inhibitor...
February 2018: Heliyon
Cristian R Astorga, Alejandro González-Candia, Alejandro A Candia, Esteban G Figueroa, Daniel Cañas, Germán Ebensperger, Roberto V Reyes, Aníbal J Llanos, Emilio A Herrera
Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs ( Ovis aries ) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters...
2018: Frontiers in Physiology
Bon-Hee Gu, Matthew C Madison, David Corry, Farrah Kheradmand
Multicellular organisms synthesize and renew components of their subcellular and scaffolding proteins, collectively known as the extracellular matrix molecules (ECMs). In the lung, ECMs maintain tensile strength, elasticity, and dictate the specialized function of multiple cell lineages. These functions are critical in lung homeostatic processes including cellular migration and proliferation during morphogenesis or in response to repair. Alterations in lung ECMs that expose cells to new cryptic fragments, generated in response to endogenous proteinases or exogenous toxins, are associated with the development of several common respiratory diseases...
March 17, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Rajesh Sinha, Pooja Singh, Neeraj K Saini, Ajit Kumar, Rakesh Pathak, Amita Chandolia, Kushal Garima, Gaurav Tyagi, Madhu Chopra, Ashok Kumar Prasad, Hanumantharao G Raj, Mridula Bose
Cholesterol, an essential cellular component in macrophages, is exploited for entry and long-term survival of Mycobacterium inside the host. Cholesterol-deficient macrophages can restrict the cholesterol-dependent entry of Mycobacterium. Rv3499c protein in Mycobacterium has high binding affinity for cholesterol. Rv3499c gene is a part of mce4 operon which is reported to act as cholesterol transport system in mycobacteria. Earlier we reported Rv3499c protein to localise on cell wall and facilitate entry of Mycobacterium inside macrophages...
March 2018: Tuberculosis
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
Yide Huang, Yafei Zhang, Lilin Ge, Yao Lin, Hang Fai Kwok
The protein tyrosine phosphatase (PTP) family is involved in multiple cellular functions and plays an important role in various pathological and physiological processes. In many chronic diseases, for example cancer, PTP is a potential therapeutic target for cancer treatment. In the last two decades, dozens of PTP inhibitors which specifically target individual PTP molecules were developed as therapeutic agents. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and is the second most lethal cancer worldwide due to a lack of effective therapies...
March 20, 2018: Cancers
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
Goro Katsuumi, Ippei Shimizu, Yohko Yoshida, Tohru Minamino
In mammals, aging is associated with accumulation of senescent cells. Stresses such as telomere shortening and reactive oxygen species induce "cellular senescence", which is characterized by growth arrest and alteration of the gene expression profile. Chronological aging is associated with development of age-related diseases, including heart failure, diabetes, and atherosclerotic disease, and studies have shown that accumulation of senescent cells has a causative role in the pathology of these age-related disorders...
2018: Frontiers in Cardiovascular Medicine
Judith A Smith
Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defense against pathogens, but when aberrantly produced, may also drive pathologic inflammation...
2018: Frontiers in Immunology
Kaori Wakabayashi, Takahiko Umahara, Katsuiku Hirokawa, Haruo Hanyu, Toshiki Uchihara
α-Synuclein shares structural homology with 14-3-3 proteins. Seven 14-3-3 protein isoforms have been identified in mammals. Among them, the 14-3-3 sigma isoform was initially considered absent in the mammalian brain. However, we previously identified immunohistochemical association of 14-3-3 sigma with Pick bodies. Because 14-3-3 isoforms other than sigma isoform have been identified in Lewy bodies, we were prompted to look for this 14-3-3 sigma-like immunoreactivity (IR) in Lewy bodies in the brainstem, cerebral cortex, and Lewy neurites in seven patients with Lewy body disease...
March 16, 2018: Neuroscience Letters
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