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Advancing the understanding of human disease

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  • Stained cells

    This collection, curated by Ho-Keung Ng of the Chinese University of Hong Kong, focuses on the underlying pathogenetic and molecular processes that contribute to brain tumors.

  • Immunofluorescent staining of human melanocytic specimens

    This Collection highlights the newest top-viewed content from Laboratory Investigation. Updated each month, we hope you enjoy reading this selection of articles. Laboratory Investigation aims to publish high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease.

  • Focus on China Collection Cover

    The editors of Laboratory Investigation are proud to present a Web Focus that showcases research by authors from institutions across China. We selected recent papers to highlight the significant contributions of Chinese scientists and to introduce the journal to an even wider audience.

  • Pseudo-color rendering of fluorescence-like representations of non-small cell lung cancer

    Brightfield microscopy is the preferred method of pathologists for diagnosing solid tumors, utilizing common staining techniques such as hematoxylin and eosin staining and immunohistochemistry. This collection of articles describe new ways to process samples and interpret data generated by histopathology and immunohistochemistry, as well as new technologies that complement these methods.

Laboratory Investigation is a Transformative Journal; authors can publish using the traditional publishing route OR via immediate gold Open Access.

Our Open Access option complies with funder and institutional requirements.

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  • PAQR3 silencing promotes skin wound healing and angiogenesis, enhanced macrophage M2 polarization and elevated expression of PPARγ in diabetic mice. PAQR3 silencing in macrophages also enhances migration of HaCaT cells and tube formation of HUVECs in vitro. The promotion of diabetic wound healing through M2 macrophage polarization and angiogenesis by PAQR3 silencing is mediated by the inhibition of STUB1-mediated PPARγ protein ubiquitination and degradation.

    • Jian Qiu
    • Chang Shu
    • Wei-Chang Zhang
    Article
  • The authors propose a new role for ADAR1, an RNA editing enzyme, in nonalcoholic fatty liver disease (NAFLD). Overexpression of ADAR1 ameliorates high-fat diet-induced liver injury and significantly abolishes NLRP3 inflammasome activation in THP-1 cells. Inhibition of ADAR1 expression causes a dramatic enhancement in NLRP3 inflammasome activation. Therefore, ADAR1 is a potential NAFLD suppressor through regulation of NLRP3 inflammasomes.

    • Rong Xiang
    • Yuxing Liu
    • Fang Wang
    Article
  • The replacement and desmoplastic histopathological growth patterns (HGP) were studied in patients with uveal melanoma liver metastases (MUM). L1CAM and laminin vascular network were detected at the advancing front of the high-risk replacement HGP but not in the more prognostically favorable desmoplastic HGP. Any percentage of replacement HGP (rHGP), predominant rHGP, or pure rHGP in MUM had a significant adverse effect on metastasis-specific overall survival (p = 0.038; (p = 0.0058); p = 0.0064

    • Raymond Barnhill
    • Steven van Laere
    • Claire Lugassy
    Article
  • Smurf1 is highly expressed in the livers of non-alcoholic fatty liver disease (NAFLD) patients and NAFLD mode mice. Smurf1 promotes p53 ubiquitynation via stabilizing mouse double minute 2 (MDM2). An decrease in p53 enhances lipogenesis by inducing SREBP-1c, and inhibits lipolysis via repressing malonyl-CoA decarboxylase (MCD) or Lipin1. Overall, Smurf1 deficiency attenuates liver steatosis via the MDM-p53 pathway.

    • Wenjun Lin
    • Xin Zhang
    • Wei An
    Article
  • The presence of visceral obesity or type 2 diabetes mellitus is a major risk factor and potential therapeutic target for non-alcoholic fatty liver disease (NAFLD). A new murine NAFLD model established in this study had obesity and insulin resistance, and rapidly develop steatohepatitis and fibrosis. This model could be useful as preclinical models for drug development of NAFLD.

    • Takafumi Sakuma
    • Masato Nakamura
    • Naoya Kato
    Article
  • Characterization of macrophage polarization into different functional phenotypes is valuable for further investigation of gout pathogenesis, as well as for a better disease management. In this study the authors found that altered macrophage polarization exists in various stages of gouty inflammation. Macrophages in acute gout were polarized into M1 at an early stage and into M2 at later stages while the macrophages in chronic gout were generally polarized towards M2. The number of M1 rose with the progression of inflammation. Early increase of M2 was observed, which might be generated directly from M0.

    • Li Zhao
    • Wenjing Ye
    • Yu Xue
    Article
  • The antibody drug conjugate (ADC) Trastuzumab deruxtecan (T-DXd) has shown activity in breast cancer with low levels of HER2 expression. The historical/conventional assays for HER2 were designed separate high levels of HER2 from intermediate levels and show no expression in the low range. In this study, we determine the optimal dynamic range for unamplified HER2 detection in breast cancer and then design a quantitative assay to stratify HER2 expression in unamplified cases. Assessment of HER2 protein in the optimal dynamic range will ultimately help select the optimal patients for T-DXd and this work can serve as a model for other assays for ADCs where pathology reads may be less accurate that protein measurements.

    • Myrto Moutafi
    • Charles J. Robbins
    • David L. Rimm
    Article
  • Apolipoprotein B100 (apoB100) is the structural protein of several of the lipoprotein cholesterol carriers and accumulates in extracellular deposits in the systemic disease atherosclerosis, and the neurodegenerative blinding disease, age-related macular degeneration. Herein, the authors characterized the retinal pathology of transgenic mice expressing mouse apoB100, in order to catalog their functional and morphological ocular phenotypes, as a function of age, and establish measurable endpoints for their use as a pre-clinical mouse model to test potential therapies.

    • Mayur Choudhary
    • Faryan Tayyari
    • Goldis Malek
    Article