9,491 results match your criteria Laboratory Investigation [Journal]


Artificial intelligence in neuropathology: deep learning-based assessment of tauopathy.

Lab Invest 2019 Feb 15. Epub 2019 Feb 15.

Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Accumulation of abnormal tau in neurofibrillary tangles (NFT) occurs in Alzheimer disease (AD) and a spectrum of tauopathies. These tauopathies have diverse and overlapping morphological phenotypes that obscure classification and quantitative assessments. Recently, powerful machine learning-based approaches have emerged, allowing the recognition and quantification of pathological changes from digital images. Read More

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http://dx.doi.org/10.1038/s41374-019-0202-4DOI Listing
February 2019

Autonomous trisomic rescue of Down syndrome cells.

Lab Invest 2019 Feb 13. Epub 2019 Feb 13.

Department of Reproductive Biology, National Center for Child Health and Development, Tokyo, 157-8535, Japan.

Down syndrome is the most frequent chromosomal abnormality among live-born infants. All Down syndrome patients have mental retardation and are prone to develop early onset Alzheimer's disease. However, it has not yet been elucidated whether there is a correlation between the phenotype of Down syndrome and the extra chromosome 21. Read More

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http://dx.doi.org/10.1038/s41374-019-0230-0DOI Listing
February 2019

Lipopolysaccharide promotes lung fibroblast proliferation through autophagy inhibition via activation of the PI3K-Akt-mTOR pathway.

Lab Invest 2019 Feb 13. Epub 2019 Feb 13.

Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Pulmonary fibrosis is a major cause of death in patients with acute respiratory distress syndrome (ARDS). Our previous study revealed that lipopolysaccharide (LPS) challenge could lead to mouse lung fibroblast proliferation. Additionally, inhibition of autophagy in lung fibroblasts was also reported to be crucial during the process of pulmonary fibrosis. Read More

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http://www.nature.com/articles/s41374-018-0160-2
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http://dx.doi.org/10.1038/s41374-018-0160-2DOI Listing
February 2019
1 Read

Transmission of α-synuclein seeds in neurodegenerative disease: recent developments.

Lab Invest 2019 Feb 13. Epub 2019 Feb 13.

Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA.

Cell-to-cell transmission of proteopathic alpha-synuclein (α-syn) seeds is increasingly thought to underlie the progression of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and related synucleinopathies. As such, it is important to understand the chemical and biological relationships between cells and pathological aggregates of α-syn. This brief review updates our understanding of the templated spread of α-syn pathology in neurodegenerative disease from the perspective of proteopathic α-syn seeds, including how these seeds are processed by cells as well as their effects on cellular function. Read More

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http://dx.doi.org/10.1038/s41374-019-0195-zDOI Listing
February 2019

The amyloid cascade and Alzheimer's disease therapeutics: theory versus observation.

Lab Invest 2019 Feb 13. Epub 2019 Feb 13.

Department of Biology and Brain Health Consortium, College of Sciences, The University of Texas at San Antonio, San Antonio, TX, USA.

The identification of amyloid-β precursor protein (APP) pathogenic mutations in familial early onset Alzheimer's disease (AD), along with knowledge that amyloid-β (Aβ) was the principle protein component of senile plaques, led to the establishment of the amyloid cascade hypothesis. Down syndrome substantiated the hypothesis, given an extra copy of the APP gene and invariable AD pathology hallmarks that occur by middle age. An abundance of support for the amyloid cascade hypothesis followed. Read More

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http://dx.doi.org/10.1038/s41374-019-0231-zDOI Listing
February 2019

DNA damage as a marker of brain damage in individuals with history of concussions.

Lab Invest 2019 Feb 13. Epub 2019 Feb 13.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Mild traumatic brain injury (mTBI) is common in many populations, including athletes, veterans, and domestic abuse victims. mTBI can cause chronic symptoms, including depression, irritability, memory problems, and attention deficits. A history of repetitive mTBI has been epidemiologically associated with developing early-onset dementia and neurodegenerative diseases and, in particular, is thought to be the underlying cause of chronic traumatic encephalopathy (CTE)-a progressive tauopathy diagnosed by the presence of perivascular hyperphosphorylated tau protein (p-tau) in the depths of cortical sulci. Read More

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http://dx.doi.org/10.1038/s41374-019-0199-8DOI Listing
February 2019

Accumulation of fructose 1,6-bisphosphate protects clear cell renal cell carcinoma from oxidative stress.

Lab Invest 2019 Feb 13. Epub 2019 Feb 13.

Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China.

Clear cell renal cell carcinoma (ccRCC) is characterized by the activation of hypoxia-inducible factors and enhanced aerobic glycolysis. In our previous study, metabolic profiling revealed a threefold increase of fructose 1,6-bisphosphate (FBP) in ccRCC tissue compared with normal kidney tissue. As an important intermediate metabolite, its role in cancer development remains unknown. Read More

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http://dx.doi.org/10.1038/s41374-019-0203-3DOI Listing
February 2019

The pathophysiological basis of vascular disease.

Lab Invest 2019 Feb 12. Epub 2019 Feb 12.

Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

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http://dx.doi.org/10.1038/s41374-019-0192-2DOI Listing
February 2019

Osteoblast lineage-specific cell-surface antigen (A7) regulates osteoclast recruitment and calcification during bone remodeling.

Lab Invest 2019 Feb 11. Epub 2019 Feb 11.

Department of Molecular Cell Biology and Oral Anatomy, Faculty of Dental Science, Kyushu University, Maidashi, Fukuoka, 812-8582, Japan.

Bone remodeling is a continuous process characterized by highly coordinated cell-cell interactions in distinct multi-cellular units. Osteoclasts, which are specialized bone resorbing cells, play a central role in bone remodeling. Although the RANKL/RANK axis determines the gross number of osteoclasts present in bone tissue, detailed molecular events regulating bone remodeling related to osteoclast recruitment, initiation of bone remodeling, and coupling of bone resorption and bone formation are still ambiguous. Read More

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http://dx.doi.org/10.1038/s41374-018-0179-4DOI Listing
February 2019

Tau and TDP-43 proteinopathies: kindred pathologic cascades and genetic pleiotropy.

Lab Invest 2019 Feb 11. Epub 2019 Feb 11.

University of Kentucky College of Medicine, Lexington, KY, USA.

We review the literature on Tau and TDP-43 proteinopathies in aged human brains and the relevant underlying pathogenetic cascades. Complex interacting pathways are implicated in Alzheimer's disease and related dementias (ADRD), wherein multiple proteins tend to misfold in a manner that is "reactive," but, subsequently, each proteinopathy may contribute strongly to the clinical symptoms. Tau proteinopathy exists in brains of individuals across a broad spectrum of primary underlying conditions-e. Read More

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http://dx.doi.org/10.1038/s41374-019-0196-yDOI Listing
February 2019
2 Reads

Association between TDP-43 and mitochondria in inclusion body myositis.

Lab Invest 2019 Feb 11. Epub 2019 Feb 11.

Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

Inclusion body myositis (IBM) is the most common cause of primary myopathy in individuals aged 50 years and over, and is pathologically characterized by protein aggregates of p62 and mislocalized cytoplasmic TDP-43, as well as mitochondrial abnormalities in affected muscle fibers. Our recent studies have shown the accumulation of TDP-43 in mitochondria in neurons from patients with amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), and revealed mitochondria as critical mediators of TDP-43 neurotoxicity. In this study, we investigated the association between mitochondria and TDP-43 in biopsied skeletal muscle samples from IBM patients. Read More

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http://dx.doi.org/10.1038/s41374-019-0233-xDOI Listing
February 2019
2 Reads

MAPT mutations, tauopathy, and mechanisms of neurodegeneration.

Lab Invest 2019 Feb 11. Epub 2019 Feb 11.

Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.

In multiple neurodegenerative diseases, including Alzheimer's disease (AD), a prominent pathological feature is the aberrant aggregation and inclusion formation of the microtubule-associated protein tau. Because of the pathological association, these disorders are often referred to as tauopathies. Mutations in the MAPT gene that encodes tau can cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), providing the clearest evidence that tauopathy plays a causal role in neurodegeneration. Read More

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http://dx.doi.org/10.1038/s41374-019-0197-xDOI Listing
February 2019

Dissecting α-synuclein inclusion pathology diversity in multiple system atrophy: implications for the prion-like transmission hypothesis.

Lab Invest 2019 Feb 8. Epub 2019 Feb 8.

Department of Pathology, University of Florida, Gainesville, FL, 32610, USA.

Synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of insoluble, aggregated α-synuclein (αS) pathological inclusions. Multiple system atrophy (MSA) presents with extensive oligodendroglial αS pathology and additional more limited neuronal inclusions while most of the other synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies (DLB), develop αS pathology primarily in neuronal cell populations. αS biochemical alterations specific to MSA have been described but thorough examination of these unique and disease-specific protein deposits is further warranted especially given recent findings implicating the prion-like nature of synucleinopathies perhaps with distinct strain-like properties. Read More

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http://dx.doi.org/10.1038/s41374-019-0198-9DOI Listing
February 2019
1 Read

Analyses of alveolar epithelial injury via lipid-related stress in mammalian target of rapamycin inhibitor-induced lung disease.

Lab Invest 2019 Feb 6. Epub 2019 Feb 6.

Department of Analytic Human Pathology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

Although mammalian target of rapamycin inhibitors (mTORi) are used to treat various malignancies, they frequently induce active alveolitis and dyslipidemia. Abnormal lipid metabolism affects alveolar surfactant function and results in pulmonary disorders; however, the pathophysiology of lung injury and its relationship with lipid metabolism remain unknown. We investigated the relationship between lipid metabolism and alveolar epithelial injury, focusing on peroxisome proliferator-activated receptor-γ (PPAR-γ) as a lipid stress-related factor in mTORi-induced lung injury. Read More

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http://dx.doi.org/10.1038/s41374-018-0158-9DOI Listing
February 2019

A pipeline for rapidly generating genetically engineered mouse models of pancreatic cancer using in vivo CRISPR-Cas9-mediated somatic recombination.

Lab Invest 2019 Feb 6. Epub 2019 Feb 6.

Department of Translational Molecular Pathology and Sheikh Ahmed Pancreatic Cancer Research Center, UT MD Anderson Cancer Center, Houston, TX, USA.

Genetically engineered mouse models (GEMMs) that recapitulate the major genetic drivers in pancreatic ductal adenocarcinoma (PDAC) have provided unprecedented insights into the pathogenesis of this lethal neoplasm. Nonetheless, generating an autochthonous model is an expensive, time consuming and labor intensive process, particularly when tissue specific expression or deletion of compound alleles are involved. In addition, many of the current PDAC GEMMs cause embryonic, pancreas-wide activation or loss of driver alleles, neither of which reflects the cognate human disease scenario. Read More

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http://dx.doi.org/10.1038/s41374-018-0171-zDOI Listing
February 2019

Let's go swimming.

Lab Invest 2019 Feb 5. Epub 2019 Feb 5.

United States and Canadian Academy of Pathology, Palm Springs, CA, USA.

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http://dx.doi.org/10.1038/s41374-019-0194-0DOI Listing
February 2019

Molecular hydrogen attenuates gefitinib-induced exacerbation of naphthalene-evoked acute lung injury through a reduction in oxidative stress and inflammation.

Lab Invest 2019 Feb 1. Epub 2019 Feb 1.

Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

Although inhibition of epidermal growth factor receptor (EGFR)-mediated cell signaling by the EGFR tyrosine kinase inhibitor gefitinib is highly effective against advanced non-small cell lung cancer, this drug might promote severe acute interstitial pneumonia. We previously reported that molecular hydrogen (H) acts as a therapeutic and preventive anti-oxidant. Here, we show that treatment with H effectively protects the lungs of mice from severe damage caused by oral administration of gefitinib after intraperitoneal injection of naphthalene, the toxicity of which is related to oxidative stress. Read More

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http://www.nature.com/articles/s41374-019-0187-z
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http://dx.doi.org/10.1038/s41374-019-0187-zDOI Listing
February 2019
4 Reads

Clinical diagnoses among individuals with primary age-related tauopathy versus Alzheimer's neuropathology.

Lab Invest 2019 Feb 1. Epub 2019 Feb 1.

National Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA.

Primary age-related tauopathy (PART) is increasingly recognized as a pathologic entity distinct from Alzheimer's disease (AD). Given that the diagnosis of PART is an autopsy diagnosis, it is unclear how PART is perceived in clinical practice. Thus, we investigated the presumptive primary and contributing diagnoses in individuals who had cognitive impairment while alive and who met neuropathologic criteria for PART at autopsy. Read More

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http://dx.doi.org/10.1038/s41374-019-0186-0DOI Listing
February 2019
1 Read

Impaired mitophagy triggers NLRP3 inflammasome activation during the progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis.

Lab Invest 2019 Jan 30. Epub 2019 Jan 30.

Shanghai Institute of Liver Diseases, Shanghai, China.

Activation of inflammation is an important mechanism in the development of nonalcoholic steatohepatitis (NASH). This study aims to delineate how mitophagy affects NLRP3 inflammasome activation in hepatic lipotoxicity. Mice were fed a high fat/calorie diet (HFCD) for 24 weeks. Read More

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http://dx.doi.org/10.1038/s41374-018-0177-6DOI Listing
January 2019

Response to: An immunohistochemical approach to detect oncogenic CTNNB1 mutations in primary neoplastic tissues.

Lab Invest 2019 Jan 30. Epub 2019 Jan 30.

Departments of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

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http://dx.doi.org/10.1038/s41374-018-0183-8DOI Listing
January 2019

Surfactant dysfunction and alveolar collapse are linked with fibrotic septal wall remodeling in the TGF-β1-induced mouse model of pulmonary fibrosis.

Lab Invest 2019 Jan 30. Epub 2019 Jan 30.

Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.

In human idiopathic pulmonary fibrosis (IPF), collapse of distal airspaces occurs in areas of the lung not (yet) remodeled. Mice lungs overexpressing transforming growth factor-β1 (TGF-β1) recapitulate this abnormality: surfactant dysfunction results in alveolar collapse preceding fibrosis and loss of alveolar epithelial type II (AE2) cells' apical membrane surface area. Here we examined whether surfactant dysfunction-related alveolar collapse due to TGF-β1 overexpression is linked to septal wall remodeling and AE2 cell abnormalities. Read More

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http://dx.doi.org/10.1038/s41374-019-0189-xDOI Listing
January 2019
1 Read

Knockout of α-calcitonin gene-related peptide attenuates cholestatic liver injury by differentially regulating cellular senescence of hepatic stellate cells and cholangiocytes.

Lab Invest 2019 Jan 30. Epub 2019 Jan 30.

Department of Medical Physiology, Texas A&M University Health Science Center, Temple, TX, USA.

α-Calcitonin gene-related peptide (α-CGRP) is a 37-amino acid neuropeptide involved in several pathophysiological processes. α-CGRP is involved in the regulation of cholangiocyte proliferation during cholestasis. In this study, we aimed to evaluate if α-CGRP regulates bile duct ligation (BDL)-induced liver fibrosis by using a α-CGRP knockout (α-CGRP) mouse model. Read More

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http://dx.doi.org/10.1038/s41374-018-0178-5DOI Listing
January 2019
1 Read

Protective effect and mechanism of IL-10 on renal ischemia-reperfusion injury.

Lab Invest 2019 Jan 30. Epub 2019 Jan 30.

Department of Hematology and Rheumatology, Kindai University School of Medicine, Osaka-Sayama, Osaka, 589-8511, Japan.

Interleukin (IL)-10, a cytokine with anti-inflammatory effects, is produced by blood cells and cells of various organs. Ischemia-reperfusion injury (IRI) is a systemic inflammatory disease caused by a systemic circulation of pro-inflammatory cytokines and chemokines produced from blood cells or organs damaged by ischemia. Apoptosis, a key event after IRI, is correlated with the degree of injury. Read More

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http://dx.doi.org/10.1038/s41374-018-0162-0DOI Listing
January 2019
1 Read

Anti-cancer effect of doxorubicin is mediated by downregulation of HMG-Co A reductase via inhibition of EGFR/Src pathway.

Lab Invest 2019 Jan 30. Epub 2019 Jan 30.

Comparative Biomedicine Research Branch, Division of Translational Science, National Cancer Center, Goyang, Korea.

Doxorubicin is a widely used DNA damage-inducing anti-cancer drug. However, its use is limited by its dose-dependent side effects, such as cardiac toxicity. Cholesterol-lowering statin drugs increase the efficacy of some anti-cancer drugs. Read More

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http://dx.doi.org/10.1038/s41374-019-0193-1DOI Listing
January 2019
3 Reads

miR-146a targeted to splenic macrophages prevents sepsis-induced multiple organ injury.

Lab Invest 2019 Jan 30. Epub 2019 Jan 30.

Department of Biochemistry, Nagoya University Graduate School of Medicine. 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, Japan.

Development of a novel agent against life-threatening sepsis requires the in-depth understanding of the relevant pathophysiology and therapeutic targets. Given the function of microRNAs (miRNAs) as potent oligonucleotide therapeutics, here we investigated the pathophysiological role of exogenously applied miRNA in sepsis-induced multiple organ injury. In vitro, miR-16, miR-126, miR-146a, and miR-200b suppressed the production of pro-inflammatory cytokines in RAW264. Read More

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http://dx.doi.org/10.1038/s41374-019-0190-4DOI Listing
January 2019

STC-1 ameliorates renal injury in diabetic nephropathy by inhibiting the expression of BNIP3 through the AMPK/SIRT3 pathway.

Lab Invest 2019 Jan 25. Epub 2019 Jan 25.

Department of Nephrology, The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, 139 Renmin Road, Changsha, Hunan, 410011, People's Republic of China.

Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in individuals with diabetes, and it is the leading cause of end-stage renal disease (ESRD) worldwide. Stanniocalcin-1 (STC-1) is present in various tissues, and it has antioxidant and anti-apoptotic activities, which play a role in kidney protection, including diabetic nephropathy (DN). However, the mechanism that underlies these effects remains unknown. Read More

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http://www.nature.com/articles/s41374-018-0176-7
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http://dx.doi.org/10.1038/s41374-018-0176-7DOI Listing
January 2019
5 Reads

Epithelial-mesenchymal transition as a mechanism of resistance to tyrosine kinase inhibitors in clear cell renal cell carcinoma.

Lab Invest 2019 Jan 25. Epub 2019 Jan 25.

Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Tyrosine kinase inhibitors (TKIs) are widely accepted as treatment for metastatic clear cell renal cell carcinoma (ccRCC). However, most patients eventually experience disease progression despite TKI treatment, even if the initial response is favorable. To define the underlying mechanism of TKI resistance, 10 TKI-treated metastatic ccRCC cases in which tumor samples were harvested before treatment and immediately after disease progression were examined. Read More

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http://dx.doi.org/10.1038/s41374-019-0188-yDOI Listing
January 2019
1 Read

Fibroblast activation protein-positive fibroblasts promote tumor progression through secretion of CCL2 and interleukin-6 in esophageal squamous cell carcinoma.

Lab Invest 2019 Jan 25. Epub 2019 Jan 25.

Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor with frequent recurrence even after curative resection. The tumor microenvironment, which consists of non-cancer cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), was recently reported to promote several cancers, including ESCC. However, the role of CAF as a coordinator for tumor progression in ESCC remains to be elucidated. Read More

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http://dx.doi.org/10.1038/s41374-018-0185-6DOI Listing
January 2019
2 Reads

Lens-specific conditional knockout of Msx2 in mice leads to ocular anterior segment dysgenesis via activation of a calcium signaling pathway.

Lab Invest 2019 Jan 25. Epub 2019 Jan 25.

Department of Ophthalmology, The Fourth Affiliated Hospital, China Medical University, 110005, Shenyang, China.

Ocular anterior segment dysgenesis (ASD) is a failure of normal development of anterior structures of the eye, leading to lens opacification. The underlying mechanisms relating to ASD are still unclear. Previous studies have implicated transcriptional factor muscle segment homeobox 2 (Msx2) in ASD. Read More

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http://dx.doi.org/10.1038/s41374-018-0180-yDOI Listing
January 2019

Preconditioned adipose-derived stem cells ameliorate cardiac fibrosis by regulating macrophage polarization in infarcted rat hearts through the PI3K/STAT3 pathway.

Lab Invest 2019 Jan 25. Epub 2019 Jan 25.

Bioinnovation Center, Tzu Chi Foundation, Hualien, Taiwan.

Stem cells can modify macrophage phenotypes; however, the mechanisms remain unclear. We investigated whether n-butylidenephthalide (BP) primed adipose-derived stem cells (ADSCs) attenuated cardiac fibrosis via regulating macrophage phenotype by a PI3K/STAT3-dependent pathway in postinfarcted rats. Male Wistar rats after coronary ligation were allocated to receive either intramyocardial injection of vehicle, ADSCs (1 × 10 cells), BP-preconditioned ADSCs, (BP + lithium)-preconditioned ADSCs, (BP + LY294002)-preconditioned ADSCs, and (BP + S3I-201)-preconditioned ADSCs. Read More

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http://dx.doi.org/10.1038/s41374-018-0181-xDOI Listing
January 2019
1 Read
3.676 Impact Factor

FOXO3 is involved in the tumor necrosis factor-driven inflammatory response in fibroblast-like synoviocytes.

Lab Invest 2019 Jan 24. Epub 2019 Jan 24.

Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, 1090, Vienna, Austria.

Fibroblast-like synoviocytes (FLS) are major contributors to joint inflammation in rheumatoid arthritis (RA). Forkhead box O 3 (FOXO3) perturbations in immune cells are increasingly linked to RA pathogenesis. Here, we show that FOXO3 is distinctly inactivated/phosphorylated in the FLS of rheumatoid synovitis. Read More

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http://www.nature.com/articles/s41374-018-0184-7
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http://dx.doi.org/10.1038/s41374-018-0184-7DOI Listing
January 2019
7 Reads

Associating liver partition and portal vein ligation for staged hepatectomy: establishment of an animal model with insufficient liver remnant.

Lab Invest 2019 Jan 21. Epub 2019 Jan 21.

Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique,Université catholique de Louvain, Brussels, Belgium.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows extended hepatectomy in patients with an extremely small future liver remnant (FLR). Current rodent models of ALPPS do not include resection resulting in insufficient-for-survival FLR, or they do incorporate liver mass reduction prior to ALPPS. Differences in FLR volume and surgical procedures could bias our understanding of physiological and hemodynamic mechanisms. Read More

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http://dx.doi.org/10.1038/s41374-018-0155-zDOI Listing
January 2019

Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis.

Lab Invest 2019 Jan 21. Epub 2019 Jan 21.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.

Homeobox B7 (HOXB7) protein is reported to be aberrantly expressed in a variety of cancers and to play an important role in multiple cellular processes. However, the specific mechanism by which HOXB7 promotes the malignant progression of intrahepatic cholangiocarcinoma (ICC) remains unclear. Therefore, we used quantitative real-time polymerase chain reaction (PCR) to detect the expression level of HOXB7 in 38 paired ICC tissue samples. Read More

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http://dx.doi.org/10.1038/s41374-018-0150-4DOI Listing
January 2019
4 Reads
3.676 Impact Factor

miR-483-5p decreases the radiosensitivity of nasopharyngeal carcinoma cells by targeting DAPK1.

Lab Invest 2019 Jan 21. Epub 2019 Jan 21.

Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong Province, People's Republic of China.

Recurrence or metastasis resulting from radioresistance are the main challenges for the treatment of nasopharyngeal carcinoma (NPC). A great deal of evidence supports the role of abnormal expression of miRNAs in radioresistance and malignancy. In some cancers, miR-483-5p is associated with inferior disease-specific survival. Read More

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http://dx.doi.org/10.1038/s41374-018-0169-6DOI Listing
January 2019
1 Read

Cyclin-dependent kinase 1 and survivin as potential therapeutic targets against nasal natural killer/T-cell lymphoma.

Lab Invest 2019 Jan 21. Epub 2019 Jan 21.

Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.

Nasal natural killer/T-cell lymphoma (NNKTL) is closely associated with Epstein-Barr virus (EBV) and is characterized by poor prognosis, resulting from rapid progression of lesions in the affected organs. Recent data have shown that NNKTL is associated with the aberrant expression of cyclin-dependent kinase 1 (CDK1) and its downstream target survivin, but little is known about the functional roles of CDK1 and survivin in NNKTL. In the current study, we show that knockdown of the EBV-encoded oncoprotein latent membrane protein 1 (LMP1) induces downregulation of CDK1 and survivin in NNKTL cells. Read More

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http://dx.doi.org/10.1038/s41374-018-0182-9DOI Listing
January 2019
1 Read

OxHDL controls LOX-1 expression and plasma membrane localization through a mechanism dependent on NOX/ROS/NF-κB pathway on endothelial cells.

Lab Invest 2019 Jan 21. Epub 2019 Jan 21.

Departamento de Ciencias Biologicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Ave. Republica 239, 8370134, Santiago, Chile.

Systemic inflammatory diseases enhance circulating oxidative stress levels, which results in the oxidation of circulating high-density lipoprotein (oxHDL). Endothelial cell function can be negatively impacted by oxHDL, but the underlying mechanisms for this remain unclear. Some reports indicate that the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is also a receptor for oxHDL. Read More

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http://dx.doi.org/10.1038/s41374-018-0151-3DOI Listing
January 2019
1 Read

Unlocking bone for proteomic analysis and FISH.

Lab Invest 2019 Jan 18. Epub 2019 Jan 18.

Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.

Bone tissue is critically lagging behind soft tissues and biofluids in our effort to advance precision medicine. The main challenges have been accessibility and the requirement for deleterious decalcification processes that impact the fidelity of diagnostic histomorphology and hinder downstream analyses such as fluorescence in-situ hybridization (FISH). We have developed an alternative fixation chemistry that simultaneously fixes and decalcifies bone tissue. Read More

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http://www.nature.com/articles/s41374-018-0168-7
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http://dx.doi.org/10.1038/s41374-018-0168-7DOI Listing
January 2019
4 Reads

High-content, cell-by-cell assessment of HER2 overexpression and amplification: a tool for intratumoral heterogeneity detection in breast cancer.

Lab Invest 2019 Jan 18. Epub 2019 Jan 18.

Laboratory of Microsystems 2, École Polytechnique Fédérale de Lausanne EPFL, Lausanne, Switzerland.

Immunohistochemistry and fluorescence in situ hybridization are the two standard methods for human epidermal growth factor receptor 2 (HER2) assessment. However, they have severe limitations to assess quantitatively intratumoral heterogeneity (ITH) when multiple subclones of tumor cells co-exist. We develop here a high-content, quantitative analysis of breast cancer tissues based on microfluidic experimentation and image processing, to characterize both HER2 protein overexpression and HER2 gene amplification at the cellular level. Read More

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http://www.nature.com/articles/s41374-018-0172-y
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http://dx.doi.org/10.1038/s41374-018-0172-yDOI Listing
January 2019
4 Reads

Glucagon-like peptide-1 receptor activation alleviates lipopolysaccharide-induced acute lung injury in mice via maintenance of endothelial barrier function.

Lab Invest 2019 Jan 18. Epub 2019 Jan 18.

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu, China.

Glucagon-like peptide-1 (GLP-1), which is well known for regulating glucose homeostasis, exhibits multiple actions in cardiovascular disorders and renal injury. However, little is known about the effect of GLP-1 receptor (GLP-1R) activation on acute lung injury (ALI). In this study, we investigated the effect of GLP-1R on ALI and the potential underlying mechanisms with the selective agonist liraglutide. Read More

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http://dx.doi.org/10.1038/s41374-018-0170-0DOI Listing
January 2019

Central cholinergic neuronal degeneration promotes the development of postoperative cognitive dysfunction.

Lab Invest 2019 Jan 9. Epub 2019 Jan 9.

Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.

Postoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality. However, its mechanism remains poorly understood. We hypothesized that central cholinergic neuronal degeneration facilitates the development of POCD. Read More

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http://www.nature.com/articles/s41374-018-0174-9
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http://dx.doi.org/10.1038/s41374-018-0174-9DOI Listing
January 2019
5 Reads

TRAF6 neddylation drives inflammatory arthritis by increasing NF-κB activation.

Lab Invest 2019 Jan 9. Epub 2019 Jan 9.

Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, 200025, Shanghai, China.

Neddylation is a process similar to ubiquitination, and is critical in various inflammatory diseases; however, its importance in the pathogenesis of inflammatory arthritis is not well understood. Here, we investigated the role of neddylation in collagen-induced arthritis (CIA) and its clinical relevance. We showed that neddylation-related genes, including NEDD8 and CULLIN-1, were significantly upregulated in inflamed arthritic synovia. Read More

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http://www.nature.com/articles/s41374-018-0175-8
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http://dx.doi.org/10.1038/s41374-018-0175-8DOI Listing
January 2019
3 Reads
3.676 Impact Factor

Spectrum of tau pathologies in Huntington's disease.

Lab Invest 2018 Dec 20. Epub 2018 Dec 20.

Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.

Huntington's disease (HD) is an autosomal dominant disorder caused by a trinucleotide expansion in the huntingtin gene. Recently, a new role for tau has been implicated in the pathogenesis of HD, whereas others have argued that postmortem tau pathology findings are attributable to concurrent Alzheimer's disease pathology. The frequency of other well-defined common age-related tau pathologies in HD has not been examined in detail. Read More

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http://dx.doi.org/10.1038/s41374-018-0166-9DOI Listing
December 2018
2 Reads

Luminex-based quantification of Alzheimer's disease neuropathologic change in formalin-fixed post-mortem human brain tissue.

Lab Invest 2018 Dec 20. Epub 2018 Dec 20.

Department of Pathology, University of Washington, Seattle, WA, 98104, USA.

The vast majority of archived research and clinical pathological specimens are stored in the form of formalin fixed, paraffin-embedded (FFPE) tissues, but, unlike fresh frozen tissue samples, highly quantitative measures in FFPE tissues are limited to immunohistochemical and immunofluorescence thresholding image analysis studies, cell counting, and ordinal ranking systems. This poses a significant obstacle for clinical investigations that aim to correlate diagnostic markers of neurodegenerative diseases like Alzheimer's disease (AD) with parameters like age, gender, drug exposures, genotype, disease stage, co-morbidities, or environmental factors. To overcome this limitation, we have developed Luminex-based techniques and protocols for the quantification of amyloid β and hyperphosphorylated Tau in FFPE brain sections. Read More

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http://dx.doi.org/10.1038/s41374-018-0165-xDOI Listing
December 2018

Rapid diagnosis of IDH1-mutated gliomas by 2-HG detection with gas chromatography mass spectrometry.

Lab Invest 2018 Dec 20. Epub 2018 Dec 20.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

The metabolic genes encoding isocitrate dehydrogenase (IDH1, 2) are frequently mutated in gliomas. Mutation of IDH defines a distinct subtype of glioma and predicts therapeutic response. IDH mutation has a remarkable neomorphic activity of converting α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG), which is now commonly referred to as an oncometabolite and biomarker for gliomas. Read More

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http://www.nature.com/articles/s41374-018-0163-z
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http://dx.doi.org/10.1038/s41374-018-0163-zDOI Listing
December 2018
3 Reads

Lysyl oxidase enzymes mediate TGF-β1-induced fibrotic phenotypes in human skin-like tissues.

Lab Invest 2018 Dec 19. Epub 2018 Dec 19.

Department of Diagnostic Sciences, Tufts University School of Dental Medicine, Boston, MA, USA.

Cutaneous fibrosis is a common complication seen in mixed connective tissue diseases. It often occurs as a result of TGF-β-induced deposition of excessive amounts of collagen in the skin. Lysyl oxidases (LOXs), a family of extracellular matrix (ECM)-modifying enzymes responsible for collagen cross-linking, are known to be increased in dermal fibroblasts from patients with fibrotic diseases, denoting a possible role of LOXs in fibrosis. Read More

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http://dx.doi.org/10.1038/s41374-018-0159-8DOI Listing
December 2018
2 Reads

miR-608 and miR-4513 significantly contribute to the prognosis of lung adenocarcinoma treated with EGFR-TKIs.

Lab Invest 2018 Dec 14. Epub 2018 Dec 14.

Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.

Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptors (EGFR) significantly prolong the survival of lung adenocarcinoma patients with sensitizing EGFR mutations. Unfortunately, 10-30% patients do not show objective responses to EGFR-TKIs, and undergo rapid disease progression during the EGFR-TKIs therapy. Single nucleotide polymorphisms (SNPs) in mature microRNA (miRNA) sequences may influence target site interactions and modulate downstream pathways, such as the EGFR pathway. Read More

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http://dx.doi.org/10.1038/s41374-018-0164-yDOI Listing
December 2018

Cytoplasmic expression of epithelial cell transforming sequence 2 in lung adenocarcinoma and its implications for malignant progression.

Lab Invest 2018 Dec 12. Epub 2018 Dec 12.

Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Epithelial cell transforming sequence 2 (ECT2), a guanine nucleotide exchange factor, is predominantly localized in the nucleus of non-transformed cells and functions to regulate cytokinesis. ECT2 is also localized in the cytoplasm of cancer cells. Aberrant cytoplasmic expression of ECT2 is thought to drive tumor growth and invasion. Read More

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http://www.nature.com/articles/s41374-018-0142-4
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http://dx.doi.org/10.1038/s41374-018-0142-4DOI Listing
December 2018
2 Reads

MicroRNA amplification and detection technologies: opportunities and challenges for point of care diagnostics.

Lab Invest 2018 Dec 12. Epub 2018 Dec 12.

Laboratory of Applied Micro and Nanotechnology (LAMINATE), Division of Microbiology and Production, National Food Institute, Technical University of Denmark, 2800 Kgs, Lyngby, Denmark.

The volume of point of care (POC) testing continues to grow steadily due to the increased availability of easy-to-use devices, thus making it possible to deliver less costly care closer to the patient site in a shorter time relative to the central laboratory services. A novel class of molecules called microRNAs have recently gained attention in healthcare management for their potential as biomarkers for human diseases. The increasing interest of miRNAs in clinical practice has led to an unmet need for assays that can rapidly and accurately measure miRNAs at the POC. Read More

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http://dx.doi.org/10.1038/s41374-018-0143-3DOI Listing
December 2018

The role of Ca in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat adjuvant arthritis.

Lab Invest 2018 Nov 28. Epub 2018 Nov 28.

The Key Laboratory of Anti-Inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Hefei, China.

Rheumatoid arthritis is an autoimmune disease with a poor prognosis. Pyroptosis is a type of proinflammatory programmed cell death that is characterised by the activation of caspase-1 and secretion of the proinflammatory cytokines interleukin (IL)-1β/18. Previous reports have shown that pyroptosis is closely related to the development of some autoimmune diseases, such as rheumatoid arthritis. Read More

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http://www.nature.com/articles/s41374-018-0135-3
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http://dx.doi.org/10.1038/s41374-018-0135-3DOI Listing
November 2018
7 Reads

The subcellular location of cyclin B1 and CDC25 associated with the formation of polyploid giant cancer cells and their clinicopathological significance.

Lab Invest 2018 Nov 28. Epub 2018 Nov 28.

Departments of Pathology, Tianjin Union Medical Center, Tianjin, 300121, China.

Polyploid giant cancer cells (PGCCs) are key contributors to cancer heterogeneity, and the formation of PGCCs is associated with changes in the expression of cell-cycle-related proteins. This study investigated the intracellular localization and expression level of multiple cell-cycle-related proteins in PGCCs derived from BT-549 and HEY cells. In addition, the formation of PGCCs and the clinicopathological significance of cell-cycle-related proteins in human breast and ovarian cancer were examined. Read More

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http://dx.doi.org/10.1038/s41374-018-0157-xDOI Listing
November 2018