9,530 results match your criteria Laboratory Investigation [Journal]


Optimized cultivation of porcine choroid plexus epithelial cells, a blood-cerebrospinal fluid barrier model, for studying granulocyte transmigration.

Lab Invest 2019 Apr 17. Epub 2019 Apr 17.

Department of Pediatrics, Pediatric Infectious Diseases, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

The blood-cerebrospinal fluid barrier (BCSFB) plays important roles during the transport of substances into the brain, the pathogenesis of central nervous system (CNS) diseases, and neuro-immunological processes. Along these lines, transmigration of granulocytes across the blood-cerebrospinal fluid (CSF) barrier (BCSFB) is a hallmark of inflammatory events in the CNS. Choroid plexus (CP) epithelial cells are an important tool to generate in vitro models of the BCSFB. Read More

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http://dx.doi.org/10.1038/s41374-019-0250-9DOI Listing

Therapeutic potential of PLK1 inhibition in triple-negative breast cancer.

Lab Invest 2019 Apr 17. Epub 2019 Apr 17.

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.

Triple negative breast cancer (TNBC) is responsible for significant number of breast cancer-associated deaths because of lacking of successful molecular-targeted therapy. To explore a therapeutic target for TNBC, we performed a siRNA-mediated knockdown screening and identified Polo-like kinase 1 (PLK1) as a potential therapeutic target for TNBC. Knockdown of PLK1 as well as a small compound inhibitor for PLK1, BI-2536, induced G2/M arrest and created polyploid cell population, shown by increased DNA content and nuclear size. Read More

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http://dx.doi.org/10.1038/s41374-019-0247-4DOI Listing
April 2019
1 Read

Autophagy-related 7 modulates tumor progression in triple-negative breast cancer.

Lab Invest 2019 Apr 15. Epub 2019 Apr 15.

Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, China Medical University;, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning Province, China.

The exact role of autophagy in breast cancers remains elusive. In this study, we explored the potential functions of autophagy-related 7 (Atg7) in breast cancer cell lines and tissues. Compared to normal breast tissue, a significantly lower expression of Atg7 was observed in triple-negative breast cancer (TNBC), but not other subtypes. Read More

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http://www.nature.com/articles/s41374-019-0249-2
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http://dx.doi.org/10.1038/s41374-019-0249-2DOI Listing
April 2019
1 Read

Micheliolide ameliorates renal fibrosis by suppressing the Mtdh/BMP/MAPK pathway.

Lab Invest 2019 Apr 11. Epub 2019 Apr 11.

Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.

Micheliolide (MCL), derived from parthenolide (PTL), is known for its antioxidant and anti-inflammatory effects and has multiple roles in inflammatory diseases and tumours. To investigate its effect on renal disease, we intragastrically administrated DMAMCL, a dimethylamino Michael adduct of MCL for in vivo use, in two renal fibrosis models-the unilateral ureteral occlusion (UUO) model and an ischaemia-reperfusion injury (IRI) model and used MCL in combination with transforming growth factor beta 1 (TGF-β1) on mouse tubular epithelial cells (mTEC) in vitro. The expression of fibrotic markers (fibronectin and α-SMA) was remarkably reduced, while the expression of the epithelial marker E-cadherin was restored after DMAMCL treatment both in the UUO and IRI mice. Read More

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http://www.nature.com/articles/s41374-019-0245-6
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http://dx.doi.org/10.1038/s41374-019-0245-6DOI Listing
April 2019
2 Reads

Inhibition of prolyl hydroxylase domain (PHD) by JTZ-951 reduces obesity-related diseases in the liver, white adipose tissue, and kidney in mice with a high-fat diet.

Lab Invest 2019 Apr 5. Epub 2019 Apr 5.

Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

The epidemic of obesity and its complications is rapidly increasing worldwide. Recent drug discoveries established the utility of prolyl hydroxylase domain (PHD) inhibitors as stabilizers of hypoxia-inducible factors (HIFs) in vivo, which are currently in human clinical studies for the treatment of anemia in chronic kidney disease (CKD). These studies suggest a role for PHD inhibitors in ameliorating obesity and hyperlipidemia. Read More

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http://dx.doi.org/10.1038/s41374-019-0239-4DOI Listing
April 2019
2 Reads

Repeat-associated non-AUG (RAN) translation: insights from pathology.

Lab Invest 2019 Mar 27. Epub 2019 Mar 27.

Center for NeuroGenetics, University of Florida, Gainesville, FL, 32610, USA.

More than 40 different neurological diseases are caused by microsatellite repeat expansions. Since the discovery of repeat-associated non-AUG (RAN) translation by Zu et al. in 2011, nine expansion disorders have been identified as RAN-positive diseases. Read More

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http://dx.doi.org/10.1038/s41374-019-0241-xDOI Listing

Human relaxin-2 attenuates hepatic steatosis and fibrosis in mice with non-alcoholic fatty liver disease.

Lab Invest 2019 Mar 27. Epub 2019 Mar 27.

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Human relaxin-2 reduces hepatic fibrosis in mice. However, the effects of relaxin-2 on hepatic steatosis and fibrosis in animals with non-alcoholic fatty liver disease (NAFLD) remain to be elucidated. C57BL/6 mice fed a high-fat diet (HFD) or methionine-choline-deficient (MCD) diet were randomly assigned to receive recombinant human relaxin-2 (25 or 75 μg/kg/day) or vehicle for 4 weeks. Read More

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http://www.nature.com/articles/s41374-019-0240-y
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http://dx.doi.org/10.1038/s41374-019-0240-yDOI Listing
March 2019
2 Reads

B7H3 regulates differentiation and serves as a potential biomarker and theranostic target for human glioblastoma.

Lab Invest 2019 Mar 26. Epub 2019 Mar 26.

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

B7H3 (CD276), a co-stimulator molecule of the cell surface B7 protein superfamily, is expressed on glioblastomas (GBM). Recently, B7H3 functions beyond immune costimulation have been demonstrated. However, the mechanisms underlying B7H3 function are diverse and not well understood. Read More

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http://dx.doi.org/10.1038/s41374-019-0238-5DOI Listing
March 2019
1 Read

Endotoxemia-induced endothelial fibrosis inhibition improves hypotension, tachycardia, multiple organ dysfunction syndrome, cytokine response, oxidative stress, and survival.

Lab Invest 2019 Mar 25. Epub 2019 Mar 25.

Facultad de Ciencias de la Vida, Universidad Andres Bello, Republica 330, 8370146, Santiago, Chile.

Sepsis syndrome is the leading cause of mortality in critically ill patients admitted to intensive care. However, current therapies for sepsis treatment are unsatisfactory, and the mortality rate is still high. The main pathological characteristics observed during sepsis syndrome and endotoxemia include hypotension, tachycardia, multiple organ dysfunction syndrome (MODS), tissue damage, and cytokine and oxidative bursts. Read More

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http://dx.doi.org/10.1038/s41374-019-0237-6DOI Listing
March 2019
1 Read

Activation of death-associated protein kinase 1 promotes neutrophil apoptosis to accelerate inflammatory resolution in acute respiratory distress syndrome.

Lab Invest 2019 Mar 25. Epub 2019 Mar 25.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Acute respiratory distress syndrome (ARDS) is a uniform progression of overwhelming inflammation in lung tissue with extensive infiltration of inflammatory cells. Neutrophil apoptosis is thought to be a significant process in the control of the resolution phase of inflammation. It has been proved that 5-Aza-2'-deoxycytidine (Aza) can inhibit cancer by activating death-associated protein kinase 1 (DAPK1) to promote apoptosis. Read More

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http://dx.doi.org/10.1038/s41374-019-0242-9DOI Listing
March 2019
1 Read

Mitochondrial localization of PABPN1 in oculopharyngeal muscular dystrophy.

Lab Invest 2019 Mar 20. Epub 2019 Mar 20.

Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder characterized by ptosis, dysphagia, and weakness of proximal limbs. OPMD is caused by the expansion of polyalanine in poly(A)-binding protein, nuclear 1 (PABPN1). Although mitochondrial abnormality has been proposed as the possible etiology, the molecular pathogenesis is still poorly understood. Read More

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http://dx.doi.org/10.1038/s41374-019-0243-8DOI Listing
March 2019
1 Read

Abstracts from USCAP 2019: Autopsy (1-36).

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Lab Invest 2019 Mar;99(Suppl 1):1-29

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http://dx.doi.org/10.1038/s41374-019-0206-0DOI Listing

Abstracts from USCAP 2019: Education (506-536).

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Lab Invest 2019 Mar;99(Suppl 1):1-30

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http://www.nature.com/articles/s41374-019-0209-x
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http://dx.doi.org/10.1038/s41374-019-0209-xDOI Listing
March 2019
4 Reads

Abstracts from USCAP 2019: Cytopathology (317-465).

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Lab Invest 2019 Mar;99(Suppl 1):1-138

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http://dx.doi.org/10.1038/s41374-019-0208-yDOI Listing

Abstracts from USCAP 2019: Informatics (1463-1508).

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Lab Invest 2019 Mar;99(Suppl 1):1-40

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http://dx.doi.org/10.1038/s41374-019-0216-yDOI Listing

Abstracts from USCAP 2019: Index of Abstract Authors.

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Lab Invest 2019 Mar;99(Suppl 1):1-37

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http://dx.doi.org/10.1038/s41374-019-0229-6DOI Listing

Abstracts from USCAP 2019: Dermatopathology (466-505).

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Lab Invest 2019 Mar;99(Suppl 1):1-31

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http://dx.doi.org/10.1038/s41374-019-0207-zDOI Listing

Abstracts from USCAP 2019: Breast Pathology (100-298).

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Lab Invest 2019 Mar;99(Suppl 1):1-178

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http://dx.doi.org/10.1038/s41374-019-0234-9DOI Listing

Abstracts from USCAP 2019: Liver Pathology (1509-1580).

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Lab Invest 2019 Mar;99(Suppl 1):1-64

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http://dx.doi.org/10.1038/s41374-019-0217-xDOI Listing

Abstracts from USCAP 2019: Endocrine Pathology (537-577).

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Lab Invest 2019 Mar;99(Suppl 1):1-31

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http://dx.doi.org/10.1038/s41374-019-0212-2DOI Listing

Abstracts from USCAP 2019: Hematopathology (1234-1434).

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Lab Invest 2019 Mar;99(Suppl 1):1-180

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http://dx.doi.org/10.1038/s41374-019-0215-zDOI Listing

Abstracts from USCAP 2019: Quality Assurance (1897-1977).

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Lab Invest 2019 Mar;99(Suppl 1):1-69

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http://dx.doi.org/10.1038/s41374-019-0228-7DOI Listing

Abstracts from USCAP 2019: Pulmonary Pathology (1803-1896).

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Lab Invest 2019 Mar;99(Suppl 1):1-76

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http://dx.doi.org/10.1038/s41374-019-0227-8DOI Listing

Abstracts from USCAP 2019: Pediatric Pathology (1771-1802).

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Lab Invest 2019 Mar;99(Suppl 1):1-27

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http://dx.doi.org/10.1038/s41374-019-0226-9DOI Listing

Abstracts from USCAP 2019: Cardiovascular Pathology (299-316).

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Lab Invest 2019 Mar;99(Suppl 1):1-16

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http://dx.doi.org/10.1038/s41374-019-0211-3DOI Listing

Abstracts from USCAP 2019: Head and Neck Pathology (1162-1233).

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Lab Invest 2019 Mar;99(Suppl 1):1-59

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http://dx.doi.org/10.1038/s41374-019-0222-0DOI Listing

Abstracts from USCAP 2019: Genitourinary Pathology (776-992).

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Lab Invest 2019 Mar;99(Suppl 1):1-173

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http://dx.doi.org/10.1038/s41374-019-0214-0DOI Listing

Abstracts from USCAP 2019: Gastrointestinal Pathology (578-775).

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Lab Invest 2019 Mar;99(Suppl 1):1-164

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http://dx.doi.org/10.1038/s41374-019-0213-1DOI Listing

Abstracts from USCAP 2019: Bone and Soft Tissue Pathology (37-99).

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Lab Invest 2019 Mar;99(Suppl 1):1-52

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http://dx.doi.org/10.1038/s41374-019-0210-4DOI Listing

Abstracts from USCAP 2019: Infectious Disease Pathology (1435-1462).

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Lab Invest 2019 Mar;99(Suppl 1):1-27

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http://dx.doi.org/10.1038/s41374-019-0223-zDOI Listing

Abstracts from USCAP 2019: Gynecologic and Obstetric Pathology (993-1161).

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Lab Invest 2019 Mar;99(Suppl 1):1-140

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http://dx.doi.org/10.1038/s41374-019-0221-1DOI Listing

Reversal of TET-mediated 5-hmC loss in hypoxic fibroblasts by ascorbic acid.

Lab Invest 2019 Mar 5. Epub 2019 Mar 5.

Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Hypoxia resulting in hypoxia-inducible factor-1 alpha (HIF-1α) induction is known to drive scar formation during cutaneous wound healing, and may be responsible for excessive fibrosis inherent to hypertrophic scars and keloids. Because epigenetic pathways play an important role in regulation of fibrosing processes, we evaluated patient scars for DNA hydroxymethylation (5-hydroxymethylcytosine; 5-hmC) status and documented a significant decrease in scar fibroblasts. To test this finding in vitro, human fibroblasts were cultured with cobalt chloride (CoCl), a known stimulant of HIF-1α. Read More

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http://dx.doi.org/10.1038/s41374-019-0235-8DOI Listing
March 2019
6 Reads
3.676 Impact Factor

Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome.

Lab Invest 2019 Feb 26. Epub 2019 Feb 26.

Department of Critical Care Medicine, The First People's Hospital of Chenzhou/ Institute of Translation Medicine, University of South China, Chenzhou, 423000, China.

Mitophagy removes dysfunctional mitochondria and is known to play an important role in the pathogenesis of several diseases; however, the role of mitophagy in acute respiratory distress syndrome (ARDS) remains poorly understood. While we have previously demonstrated that polydatin (PD) improves lipopolysaccharide (LPS)-induced ARDS, the specific mechanism remains unclear. In present study, we aimed to determine whether PD activates Parkin-dependent mitophagy to protect against LPS-induced mitochondria-dependent apoptosis and lung injury. Read More

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http://dx.doi.org/10.1038/s41374-019-0191-3DOI Listing
February 2019
6 Reads

The beneficial effects of physical exercise in the brain and related pathophysiological mechanisms in neurodegenerative diseases.

Lab Invest 2019 Feb 26. Epub 2019 Feb 26.

Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR.

Growing evidence has shown the beneficial influence of exercise on humans. Apart from classic cardioprotection, numerous studies have demonstrated that different exercise regimes provide a substantial improvement in various brain functions. Although the underlying mechanism is yet to be determined, emerging evidence for neuroprotection has been established in both humans and experimental animals, with most of the valuable findings in the field of mental health, neurodegenerative diseases, and acquired brain injuries. Read More

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http://dx.doi.org/10.1038/s41374-019-0232-yDOI Listing
February 2019
2 Reads

Opposing roles of TCF7/LEF1 and TCF7L2 in cyclin D2 and Bmp4 expression and cardiomyocyte cell cycle control during late heart development.

Lab Invest 2019 Feb 18. Epub 2019 Feb 18.

Department of Laboratory Medicine and Pathology, University of Minnesota, Room 293, Dwan Variety Club Cardiovascular Research Center, 425 E River Pkwy, Minneapolis, MN, 55455, USA.

Bone morphogenetic protein (BMP) and Wnt pathways regulate cell proliferation and differentiation, but how these two pathways interact and mediate their nuclear actions in the heart, especially during late cardiac development, remains poorly defined. T-cell factor (TCF) and lymphoid enhancer factor (LEF) family transcriptional factors, including Lef1, Tcf7, Tcf7l1, and Tcf7l2, are important nuclear mediators of canonical Wnt/β-catenin signaling throughout cardiac development. We reveal that these TCF/LEF family members direct heart maturation through distinct temporal and spatial control. Read More

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http://dx.doi.org/10.1038/s41374-019-0204-2DOI Listing
February 2019

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
1 Read

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
3 Reads

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
14 Reads

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
1 Read

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
2 Reads

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
1 Read

The pathophysiological basis of vascular disease.

Lab Invest 2019 Mar 12;99(3):284-289. 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

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
1 Read

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
17 Reads