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American Journal of Pathology

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https://www.readbyqxmd.com/read/29353062/microrna-in-rat-liver-sinusoidal-endothelial-cells-and-hepatocytes-and-application-to-circulating-biomarkers-that-discern-pathogenesis-of-liver-injuries
#1
Shingo Oda, Masaki Takeuchi, Sho Akai, Yuji Shirai, Koichi Tsuneyama, Tsuyoshi Yokoi
Sinusoidal obstruction syndrome is a serious liver injury caused by toxic injury to liver sinusoidal endothelial cells (LSECs) during clinical chemotherapy. Although circulating microRNAs (miRNAs), such as hepatocyte-specific miR-122-5p and miR-192-5p, have been proposed as potential noninvasive biomarkers of hepatocellular liver injury, these miRNAs may not be specific to damage to other hepatic cell types, including LSECs. Here, we characterized miRNA expression in LSECs and hepatocytes and investigated whether cell type-specific miRNAs in plasma can discern pathogenesis of liver injuries in rats...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29353061/next-generation-sequencing-to-detect-deletion-of-rb1-and-erbb4-genes-in-chromophobe-renal-cell-carcinoma-a-potential-role-in-distinguishing-chromophobe-renal-cell-carcinoma-from-renal-oncocytoma
#2
Qingqing Liu, Kristine M Cornejo, Liang Cheng, Lloyd Hutchinson, Mingsheng Wang, Shaobo Zhang, Keith Tomaszewicz, Ediz F Cosar, Bruce A Woda, Zhong Jiang
Overlapping morphological, immunohistochemical, and ultrastructural features make it difficult to diagnose chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). Since ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to identify genetic markers that distinguish ChRCC from RO by using next-generation sequencing (NGS). NGS for hotspot mutations or gene copy number changes was performed on 12 renal neoplasms including seven ChRCC and five RO cases...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29353060/parathyroid-hormone-related-protein-contributes-to-early-healing-of-habu-snakevenom-induced-glomerulonephritis-in-mice
#3
Mazène Hochane, Denis Raison, Catherine Coquard, Claire Béraud, Sabrina Danilin, Audrey Bethry, Thierry Massfelder, Mariette Barthelmebs
Proliferative glomerulonephritis is characterized by local inflammation and mesangial cell deterioration, followed by mesangial proliferation and glomerular healing. Parathyroid-hormone-related peptide (PTHrP) is a mesangial cytokine-like growth factor implicated in mesangial proliferation and survival. No data are available about its role in glomerulonephritis. Herein, we analyzed the expression and role of PTHrP in glomerular inflammation and healing in an experimental model of glomerulonephritis induced by intravenous injection of Habu-snake venom in mice...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29353059/ask-family-kinases-are-required-for-optimal-nlrp3-inflammasome-priming
#4
David E Place, Parimal Samir, Rajendra Karki, Benoit Briard, Peter Vogel, Thirumala-Devi Kanneganti
Activation of the multimeric inflammasome complex leads to inflammatory responses to biotic and abiotic triggers. The inflammasome sensor, Nod-like receptor family Pyrin domain containing 3 (NLRP3), is activated by a range of stimuli and is tightly regulated to restrict excessive inflammation. Because NLRP3 responds broadly to cellular insults and regulates cell death similar to the stress-activated apoptosis signal-regulating kinases 1 and 2 (ASK1/2), we hypothesized that ASK1/2 may regulate NLRP3 activity...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29353058/chd7-is-critical-for-early-t-cell-development-and-thymus-organogenesis-in-zebrafish
#5
Zhi-Zhi Liu, Zi-Long Wang, Tae-Ik Choi, Wen-Ting Huang, Han-Tsing Wang, Ying-Ying Han, Lou-Yin Zhu, Hyun-Taek Kim, Jung-Hwa Choi, Jin-Soo Lee, Hyung-Goo Kim, Jian Zhao, Yue Chen, Zhuo Lu, Xiao-Li Tian, Bing-Xing Pan, Bao-Ming Li, Cheol-Hee Kim, Hong Xu
CHARGE syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T-cells have been noted in CHARGE syndrome. However, the mechanisms underlying T-lymphopenia are largely unexplored. Here, we observed dramatic decrease of T cells in both chd7-knockdown and -knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T cell decrease...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29353057/mechanisms-of-enhanced-osteoclastogenesis-in-alkaptonuria
#6
Giacomina Brunetti, Albina Tummolo, Gabriele D'Amato, Alberto Gaeta, Federica Ortolani, Laura Piacente, Paola Giordano, Silvia Colucci, Maria Grano, Francesco Papadia, Maria Felicia Faienza
Alkaptonuria (AKU) is a rare disorder characterized by the deficiency of the enzyme homogentisate 1,2-dioxygenase and consequent homogentisate accumulation, which leads to progressive and severe osteoarthopathy starting from the second decade of life. Thus, in AKU patients bone involvement represents an important clinical issue, which we investigated. Serum levels of RANKL, osteoprotegerin, sclerostin, DKK1, and bone remodeling markers were measured in nine AKU patients (two children and seven adults) and 22 controls, together with lumbar spine bone mineral density (LS-BMD) and femoral-BMD...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29341889/adventitial-activation-in-the-pathogenesis-of-injury-induced-arterial-remodeling-potential-implications-in-transplant-vasculopathy
#7
REVIEW
Jianli Wang, Yuan Wang, Jingjing Wang, Xiaosun Guo, Elsa C Chan, Fan Jiang
Transplant vasculopathy is one of the major causes of chronic rejection following solid organ transplantation. The pathogenic mechanisms of transplant vasculopathy are still poorly understood. Here we summarize current evidence suggesting that activation of the tunica adventitia may be involved in the pathogenesis of transplant vasculopathy. Adventitia is an early responder to various vascular injuries and plays an integral role in eliciting vascular inflammation and remodeling. Accumulation of macrophages in the adventitia promotes the development of vascular remodeling by releasing a variety of paracrine factors that have profound impacts on vascular mural cells...
January 13, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29341888/protection-against-the-neurotoxic-effects-of-%C3%AE-amyloid-peptide-on-cultured-neuronal-cells-by-lovastatin-involves-elevated-expression-of-%C3%AE-7-nicotinic-acetylcholine-receptors-and-activating-phosphorylation-of-protein-kinases
#8
Liang Zhao, Yan Xiao, Jin Xiu, Long-Chun Tan, Zhi-Zhong Guan
The treatment of neurodegenerative diseases with statins has drawn increasing attention, but the related molecular mechanisms remain elusive. To examine the pleiotropic cholesterol-independent effects of statins in connection with the treatment of Alzheimer disease, we probed the influence of lovastatin on the metabolism of amyloid precursor protein (APP) , expression of nicotinic acetylcholine receptors (nAChRs), and activity of mitogen-activated protein kinase in primary cultured neurons and SH-SY5Y cells over-expressing human APP670/671...
January 13, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29339090/patched-1-expression-correlates-with-biochemical-relapse-in-high-risk-prostate-cancer-patients
#9
Annelies Gonnissen, Sofie Isebaert, Christiaan Perneel, Chad M McKee, Filip Van Utterbeeck, Evelyne Lerut, Clare Verrill, Richard J Bryant, Steven Joniau, Ruth J Muschel, Karin Haustermans
There is an unmet clinical need for adequate biomarkers to aid risk stratification and management of prostate cancer (PCa) patients. Even within the high-risk PCa category not all patients will invariably have a poor prognosis, and improved stratification of this heterogeneous group is needed. In this context, components of the hedgehog (Hh) pathway may have promise as biomarkers, as the available evidence suggests increased Hh pathway activity may confer a poorer outcome in advanced and castrate-resistant PCa...
January 12, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29331321/this-month-in-ajp
#10
(no author information available yet)
The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
January 10, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29331492/prognostic-value-of-the-expression-of-dna-repair-related-biomarkers-mediated-by-alcohol-in-gastric-cancer-patients
#11
Yiyin Zhang, Hongyang Wu, Feng Yang, Jie Ning, Min Li, Chenchen Zhao, Shuping Zhong, Kangsheng Gu, Hua Wang
Alcohol consumption likely induces gastric carcinogenesis through deregulation of RNA polymerase (Pol) III genes and oxidative damage. Transcription factor IIB-related factor 1 (BRF1) overexpression alleviates RNA Pol III transcription inhibition through breast cancer susceptibility gene 1 (BRCA1). Myeloperoxidase (MPO) involvement in cancer is induced by alcohol-mediated oxidative damage. BRCA1/2 and MPO play key roles in DNA repair. BRCA1 and BRCA2 exert different roles in homologous recombination repair...
January 5, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29309745/alterations-of-ocular-hemodynamics-impair-ophthalmic-vascular-and-neuroretinal-function
#12
Shu-Huai Tsai, Wankun Xie, Min Zhao, Robert H Rosa, Travis W Hein, Lih Kuo
Hypertension is associated with numerous diseases, but its direct impact on the ocular circulation and neuroretinal function remains unclear. Herein, mouse eyes were challenged with different levels of hemodynamic insult via transverse aortic coarctation, which increased blood pressure and flow velocity by 50% and 40%, respectively, in the right common carotid artery, and reduced those parameters by 30% and 40%, respectively, in the left common carotid artery. Blood velocity in the right central retinal artery gradually increased up to 40% at four weeks of transverse aortic coarctation, and the velocity in the left central retinal artery gradually decreased by 20%...
January 5, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29305319/role-of-a-kinase-anchoring-protein-phosphorylation-in-alcohol-induced-liver-injury-and-hepatic-stellate-cell-activation
#13
Komal Ramani, Maria Lauda Tomasi, Joshua Berlind, Nirmala Mavila, Zhaoli Sun
Alcoholic liver injury is associated with hepatic stellate cell (HSC) activation. A-kinase anchoring protein 12 (AKAP12) scaffolds protein kinase C (PKC-α) and cyclin-D1, which is regulated by its phosphorylation, and spatiotemporally controls cell proliferation, invasiveness, and chemotaxis. HSC activation induces AKAP12 expression but the role of AKAP12's scaffolding activity in liver function is unknown. Since AKAP12 phosphorylation is enhanced in ethanol-treated HSCs, we examined AKAP12's scaffolding functions in alcohol-mediated HSC activation and liver injury...
January 2, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29294300/the-effects-of-systemic-therapy-of-pegylated-nell-1-on-fracture-healing-in-mice
#14
Justine Tanjaya, Elizabeth L Lord, Chenchao Wang, Yulong Zhang, Jong Kil Kim, Alan Nguyen, Llyod Baik, Hsin Chuan Pan, Eric Chen, Jin Hee Kwak, Xinli Zhang, Benjamin Wu, Chia Soo, Kang Ting
Fractures are common with an incidence of 13.7 per 1000 adults annually. Systemic agents have been widely used for enhancing bone regeneration; however, the efficacy of these therapeutics for the management and prevention of fracture remains unclear. NELL-1 is a potent pro-osteogenic cytokine that has been modified with PEGylation (PEGylated NELL-1; NELL-PEG) to enhance its pharmacokinetics for systemic therapy. Our aim was to investigate the effects of systemic administration of NELL-PEG on fracture healing in mice and on overall bone properties in uninjured bones...
December 30, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29269120/mouse-metanephric-mesenchymal-cell-derived-angioblasts-undergo-vasculogenesis-in-three-dimensional-culture
#15
Mandakini Patel, Chakradhar Velagapudi, Hannah Burns, Robert Doss, Myung-Ja Lee, Meenalakshmi M Mariappan, Brent Wagner, Mazen Arar, Veronique L Barnes, Hanna E Abboud, Jeffrey L Barnes
In vitro models for the investigation of renal vascular development are limited. We previously showed that isolated metanephric mesenchymal (MM) and ureteric bud (UB) cells grown in three-dimensional (3D) matrices formed organoids consisting of primitive vascular structures surrounding a polarized epithelium. Here, we examined the potential of two principal effectors of vasculogenesis, vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor B chain (PDGF-BB), to stimulate MM cell differentiation...
December 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29253460/microrna-31-3p-is-involved-in-substance-p-sp-associated-inflammation-in-human-colonic-epithelial-cells-and-experimental-colitis
#16
Kai Fang, Ivy Ka Man Law, David Padua, Aristea Sideri, Vanessa Huang, Christopher G Kevil, Dimitrios Iliopoulos, Charalabos Pothoulakis
Substance P (SP) mediates colitis. SP signaling regulates the expression of several microRNAs (miRNAs), including miR-31-3p, in human colonocytes. However, the role of miR-31-3p in colitis and the underlying mechanisms has not been elucidated. We performed real time PCR analysis of miR-31-3p expression in human colonic epithelial cells overexpressing neurokinin-1 receptor (NCM460 NK-1R) in response to SP stimulation and in NCM460 cells following interleukin (IL)-6, IL8, tumor necrosis factor (TNF)-α, and interferon-γ exposure...
December 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29253459/fibrosis-in-preeclamptic-placentas-is-associated-with-stromal-fibroblasts-activated-by-the-transforming-growth-factor-beta-1-tgfb1-signaling-pathway
#17
Takako Ohmaru-Nakanishi, Kazuo Asanoma, Mai Fujikawa, Yasuyuki Fujita, Hiroshi Yagi, Ichiro Onoyama, Nobuhiro Hidaka, Kenzo Sonoda, Kiyoko Kato
Although fibrosis is one of the most prominent pathological features of preeclamptic (PE) placentas, its mechanism remains largely unknown. Consistent with previous reports, we observed overexpression of collagen; actin, alpha 2, smooth muscle, aorta; connective tissue growth factor; and fibronectin in PE placentas compared with control ones. To investigate the mechanism of fibrosis in PE placentas, placental fibroblasts were isolated from PE placentas or normal pregnancies at delivery. The expression of fibrosis-related factors in fibroblasts was evaluated by real-time reverse transcription PCR, western blotting, ELISA, and gene microarrays...
December 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29248462/fibroblasts-promote-inflammation-and-pain-via-interleukin-1%C3%AE-induction-of-the-monocyte-chemoattractant-ccl2
#18
Hannah Louise Paish, Nicolas Stewart Kalson, Graham Robert Smith, Alicia Del Carpio Pons, Thomas Edward Baldock, Nicholas Smith, Katarzyna Swist-Szulik, David John Weir, Michelle Bardgett, David John Deehan, Derek Austin Mann, Lee Anthony Borthwick
Fibroblasts persist within fibrotic scar tissue and exhibit considerable phenotypic and functional plasticity. Here, we hypothesized that scar-associated fibroblasts may be a source of stress-induced inflammatory exacerbations and pain. To test this idea we used a human model of surgery-induced fibrosis, total knee arthroplasty (TKA). Using a combination of tissue protein expression profiling and bioinformatics we discovered that many months following TKA the fibrotic joint exists in a state of unresolved chronic inflammation...
December 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29248461/knockout-of-l-histidine-decarboxylase-hdc-prevents-cholangiocyte-damage-and-hepatic-fibrosis-in-mice-subjected-to-high-fat-diet-feeding-via-disrupted-histamine-leptin-signaling
#19
Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Jennifer Bailey, Wasim Dar, Kishore Polireddy, Qingzheng Chen, Moises I Nevah Rubin, Amelia Sybenga, Sharon DeMorrow, Fanyin Meng, Lindsey Stockton, Gianfranco Alpini, Heather Francis
Administration of a high-fat diet (HFD) coupled with sugar, mimicking a Western diet, causes fatty liver disease in mice. Histamine induces biliary proliferation and fibrosis, and regulates leptin signaling. Wild-type (WT) and l-histidine decarboxylase (Hdc-/-) mice were fed a control diet or a HFD coupled with a high fructose corn syrup equivalent. H&E and Oil Red O staining were performed to determine steatosis. Intrahepatic biliary mass and cholangiocyte proliferation were evaluated by immunohistochemistry...
December 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29248460/%C3%AE-%C3%AE-t-cells-contribute-to-injury-in-the-developing-brain
#20
Anna-Maj Albertsson, Xiaoli Zhang, Regina Vontell, Dan Bi, Roderick T Bronson, Veena Supramaniam, Ana A Baburamani, Sha Hua, Arshed Nazmi, Susanna Cardell, Changlian Zhu, Harvey Cantor, Carina Mallard, Henrik Hagberg, Jianmei W Leavenworth, Xiaoyang Wang
Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurological disabilities. Inflammation contributes to the development of perinatal brain injury, but the essential mediators leading to brain injury in early life remain largely unknown. Neonates have reduced capacity for mounting conventional αβT-cell responses. However γδT-cells are already functionally competent during early development and are important in early life immunity. We investigated the potential contribution of γδT-cells to preterm brain injury by using postmortem brains from human preterm infants with periventricular leukomalacia and two animal models of preterm brain injury-the hypoxic-ischemic mouse model and a fetal sheep asphyxia model...
December 14, 2017: American Journal of Pathology
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