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Am J Pathol 2022 Jun 22. Epub 2022 Jun 22.

Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio. Electronic address:

Organoid culture is an approach that allows three-dimensional growth for stem cells to self-organize and develop multicellular structures. Intestinal organoids have been widely used to study cellular or molecular processes in stem cell and cancer research. These cultures possess the ability to maintain cellular complexity as well as recapitulate many properties of the human intestinal epithelium, thereby providing an ideal in vitro model to investigate cellular and molecular signaling pathways. Read More

Am J Pathol 2022 Jun 22. Epub 2022 Jun 22.

Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, 70112. Electronic address:

Extracellular vesicles are generated by cells in the form of exosomes, microvesicles and apoptotic bodies. They can be taken by neighboring cells and their contents can have functional impact on cells that engulf them. As the mediators of intercellular communication, extracellular vesicles can play important roles in both physiological and pathological contexts. Read More

Am J Pathol 2022 Jun 21. Epub 2022 Jun 21.

Otolaryngology Institute of Shanghai Jiao Tong University, the Department of Otolaryngology-Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Vestibular schwannomas (VSs), which develop from Schwann cells (SCs) of the vestibular nerve, are the most prevalent benign tumors of the cerebellopontine angle and internal auditory canal. Despite advances in treatment, the cellular components and mechanisms of VS tumor progression remain unclear. Here, we performed single-cell RNA-seq on clinically surgically isolated VS samples and clarified their cellular composition in a sophisticated manner, including the heterogeneous Schwann cell subtypes. Read More

Am J Pathol 2022 Jun 22. Epub 2022 Jun 22.

Office of Research and Development, Veterans Health Administration, Washington, District of Columbia; Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland. Electronic address:

Although issues associated with returning individual research results to study participants have been well explored, these issues have been less thoroughly investigated in vulnerable individuals and populations. Considerations regarding return of research results to these individuals and populations, including how best to ensure truly informed consent, how to minimize the risks and benefits of the return of research results, and how best to ensure justice, may differ from those of the population at large. In this article, we discuss the issues and challenges associated with the return of individual research results (such as genomic, proteomic, or other biomarker data) to potentially vulnerable individuals and populations, including those who may be vulnerable for cognitive, communicative, institutional, social, deferential, medical, economic, or social reasons. Read More

Am J Pathol 2022 Jun 21. Epub 2022 Jun 21.

Temasek Life Sciences Laboratory, Singapore; Pathnova Laboratories Pte. Ltd., 1 Research Link, #05-40, Singapore 117604; Department of Biological Sciences, National University of Singapore, Singapore. Electronic address:

The detection of serum antibodies to Epstein-Barr Virus proteins by immunofluorescence assay (IFA) is considered the gold standard for nasopharyngeal cancer (NPC) screening in high-risk populations. Given the high survival rates of early asymptomatic patients compared to the poor prognosis for late-stage NPC, IFA has tremendous life-saving potential for general population screening. However, IFA requires visual interpretation of cellular staining patterns by trained pathology staff, making it labor-intensive and hence unscalable. Read More

Am J Pathol 2022 Jun 21. Epub 2022 Jun 21.

Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, Pekařská 53, 656 91 Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. Electronic address:

Toll-like receptor 3 (TLR3) is an endosomal receptor expressed in several immune and epithelial cells. Recent studies have highlighted its expression also in solid tumours, including prostate cancer (PCa), and described its role mainly in the pro-inflammatory response and induction of apoptosis. It has been found upregulated in some castration-resistant prostate cancers. Read More

Am J Pathol 2022 Jun 21. Epub 2022 Jun 21.

Department of Gastroenterology and Hepatology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.

Along with a recent remarkable decrease in Helicobacter pylori (Hp)-infected individuals, reports of gastric neoplasms in Hp-naïve patients have been increasing. A sporadic foveolar-type gastric adenoma (FGA) is one such type, and we recently reported that occurrence of this tumor is not rare in Hp-naïve gastric mucosa and its raspberry-like appearance. This study was conducted to investigate the genomic features of sporadic FGA. Read More

Am J Pathol 2022 Jun 16. Epub 2022 Jun 16.

Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

Nonalcoholic fatty liver disease (NAFLD) is an epidemic affecting 30% of the US population. NAFLD is characterized by insulin resistance and by defective lipid metabolism and mitochondrial dysfunction in the liver. SLC25A34 is a major repressive target of miRNA-122, a miRNA that has a central role in NAFLD and liver cancer. Read More

Am J Pathol 2022 Jun 17. Epub 2022 Jun 17.

Department of Head and Neck Surgery & Communication Sciences, Duke University School of Medicine, Durham, North Carolina; Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.

The tumor microenvironment (TME) plays an important role in the progression of head and neck squamous cell carcinoma (HNSCC). Currently, pathologic assessment of TME is nonstandardized and subject to observer bias. Genome-wide transcriptomic approaches to understanding the TME, while less subject to bias, are expensive and not currently a part of the standard of care for HNSCC. Read More

Am J Pathol 2022 Jun 14. Epub 2022 Jun 14.

Am J Pathol 2022 Jun 13. Epub 2022 Jun 13.

Renal Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; Veterans Affairs Boston Healthcare System, Boston, Massachusetts; Institute of Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts. Electronic address:

Aberrant hyperactivation of Wnt signaling, driven by nuclear β-catenin in the colonic epithelium, represents the seminal event in the initiation and progression of colorectal cancer (CRC). Despite its established role in CRC tumorigenesis, clinical translation of Wnt inhibitors remains unsuccessful. Late SV40 factor (LSF; encoded by TFCP2) is a transcription factor and a potent oncogene. Read More

Am J Pathol 2022 Jun 1. Epub 2022 Jun 1.

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. Electronic address:

Wound healing typically recruits the immune and vascular systems to restore tissue structure and function. However, injuries to the enthesis, a hypocellular and avascular tissue, often result in fibrotic scar formation and loss of mechanical properties, severely affecting musculoskeletal function and life quality. This raises questions about the healing capabilities of the enthesis. Read More

Am J Pathol 2022 May 29. Epub 2022 May 29.

Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Institute of Pathology, Hannover Medical School, Hannover, Germany.

Alveolar capillary dysplasia (ACD) is a rare lung developmental disorder leading to persistent pulmonary arterial hypertension and fatal outcomes in newborns. In this study, we analyzed the microvascular morphology and the underlying molecular background of ACD. One ACD group (n = 7), one pulmonary arterial hypertension group (n = 20), and one healthy control group (n = 16) were generated. Read More

Am J Pathol 2022 May 28. Epub 2022 May 28.

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Herein, we report that hairy and enhancer of split homolog-1 (HES1), known to repress gene transcription in progenitor cells of several cell lineages, is strongly expressed in cells and tissues of T-cell lymphoma expressing the oncogenic chimeric tyrosine kinase nucleophosmin (NPM)-anaplastic lymphoma kinase [ALK; ALK T-cell lymphoma (TCL)]. The structure analysis of the Orange domain of HES1 indicates that HES1 forms a highly stable homodimer. Of note, repression of HES1 expression leads to inhibition of ALK TCL cell growth in vivo. Read More

Am J Pathol 2022 May 28. Epub 2022 May 28.

Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address:

Cholangiocarcinoma (CCA) is the second most common primary liver tumor and has been associated with a late diagnosis, limited treatment options, and a 5-year survival rate of around 30%. CCA cell lines were first established in 1971, and since then, only 70 to 80 CCA cell lines have been established. These cell lines have been essential in basic and translational research to understand and identify novel mechanistic pathways, biomarkers, and disease-specific genes. Read More

Am J Pathol 2022 May 28. Epub 2022 May 28.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.

Apart from autopsy, tissue correlates of coronavirus disease 2019 (COVID-19) clinical stage are lacking. Cutaneous punch biopsy specimens of 15 individuals with severe/critical COVID-19 and six with mild/moderate COVID-19 were examined. Evidence for arterial and venous microthrombi, deposition of C5b-9 and MASP2 (representative of alternative and lectin complement pathways, respectively), and differential expression of interferon type I-driven antiviral protein MxA (myxovirus resistance A) versus SIN3A, a promoter of interferon type I-based proinflammatory signaling, were assessed. Read More

Am J Pathol 2022 May 20. Epub 2022 May 20.

Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida; Sylvester Comprehensive Cancer Centre, Miami, Florida. Electronic address:

Opioids are the gold standard for chronic and acute pain management; however, their consequence on gastric function is relatively understudied. Opioid users have a higher incidence of gastric dysfunction, worse quality of life, increased hospitalizations, and increased use of antiemetic and pain modulator medications. In the current study, we show that morphine treatment in the murine model results in greater disruption of gastric epithelial cell morphology, increased gastric cell apoptosis, elevated inflammatory cytokines, and matrix metallopeptidase-9 secretion. Read More

Am J Pathol 2022 May 21. Epub 2022 May 21.

Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau and Biomedical Research Institute Sant Pau, Departament de Medicina, Universitat Autònoma de Barcelona, Spain; John Walton Muscular Dystrophy Research Center, Newcastle University Translational and Clinical Research Institute, Newcastle Upon Tyne, United Kingdom; Centro de Investigaciones Biomédicas en Red en Enfermedades Raras (CIBERER), Madrid, Spain. Electronic address:

Late-onset Pompe disease (LOPD) is a rare genetic disorder produced by mutations in the GAA gene and is characterized by progressive muscle weakness. LOPD muscle biopsies show accumulation of glycogen along with the autophagic vacuoles associated with atrophic muscle fibers. The expression of molecules related to muscle fiber atrophy in muscle biopsies of LOPD patients was studied using immunofluorescence and real-time PCR. Read More

Am J Pathol 2022 Jul 14;192(7):986-989. Epub 2022 May 14.

Department of Surgery, University of Colorado Denver, Aurora, Colorado. Electronic address:

Am J Pathol 2022 Jul 12;192(7):985. Epub 2022 May 12.

Am J Pathol 2022 Jul 28;192(7):1066-1082. Epub 2022 Apr 28.

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky; Department of Pharmacology and Toxicology, University of Louisville Alcohol Center, Louisville, Kentucky; University of Louisville Alcohol Center, University of Louisville School of Medicine, Louisville, Kentucky; University of Louisville Hepatobiology and Toxicology Center, University of Louisville School of Medicine, Louisville, Kentucky. Electronic address:

Alcohol-associated liver disease is a global health care burden, with alcohol-associated cirrhosis (AC) and alcohol-associated hepatitis (AH) being two clinical manifestations with poor prognosis. The limited efficacy of standard of care for AC and AH highlights a need for therapeutic targets and strategies. The current study aimed to address this need through the identification of hepatic proteome and phosphoproteome signatures of AC and AH. Read More

Am J Pathol 2022 Jul 29;192(7):1053-1065. Epub 2022 Apr 29.

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Cardiac allograft vasculopathy (CAV) limits the long-term success of heart transplants. Generation of donor-specific antibodies (DSAs) is associated with increased incidence of CAV clinically, but mechanisms underlying development of this pathology remain poorly understood. Major histocompatibility complex-mismatched A/J cardiac allografts in B6. Read More

Am J Pathol 2022 Jul 25;192(7):990-1000. Epub 2022 Apr 25.

Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia; School of Medical Diagnostic and Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, Virginia.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, alcohol consumption increased markedly. Nearly one in four adults reported drinking more alcohol to cope with stress. Chronic alcohol abuse is now recognized as a factor complicating the course of acute respiratory distress syndrome and increasing mortality. Read More

Am J Pathol 2022 Jul 22;192(7):1001-1015. Epub 2022 Apr 22.

Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York; Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York. Electronic address:

Vascular injury is a well-established, disease-modifying factor in acute respiratory distress syndrome (ARDS) pathogenesis. Recently, coronavirus disease 2019 (COVID-19)-induced injury to the vascular compartment has been linked to complement activation, microvascular thrombosis, and dysregulated immune responses. This study sought to assess whether aberrant vascular activation in this prothrombotic context was associated with the induction of necroptotic vascular cell death. Read More

Am J Pathol 2022 Jul 21;192(7):1016-1027. Epub 2022 Apr 21.

Institute of Cardiovascular Science, Translational Medicine Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, China; Department of Laboratory Animal Science, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China. Electronic address:

Mediator 1 (MED1), a key subunit of the mediator complex, interacts with various nuclear receptors and functions in lipid metabolism and energy homeostasis. Dilated cardiomyopathy-related ventricular dilatation and heart failure have been reported in mice with cardiomyocyte-specific Med1 deficiency. However, the contribution of macrophage-specific MED1 in cardiac remodeling remains unclear. Read More

Am J Pathol 2022 Jul 21;192(7):1083-1091. Epub 2022 Apr 21.

SINO-US Diagnostics Lab, Tianjin Enterprise Key Laboratory of AI-aided Hematopathology Diagnosis, Tianjin, China; AI Diagnosis Lab, Shenzhen, China. Electronic address:

Chronic myeloid leukemia (CML) is a clonal proliferative disorder of granulocytic lineage, with morphologic evaluation as the first step for a definite diagnosis. This study developed a conditional generative adversarial network (cGAN)-based model, CMLcGAN, to segment megakaryocytes from myeloid cells in bone marrow biopsies. After segmentation, the statistical characteristics of two types of cells were extracted and compared between patients and controls. Read More

Am J Pathol 2022 Jul 20;192(7):1092-1108. Epub 2022 Apr 20.

Department of Cardiovascular Sciences, Lemole Center for Integrated Lymphatics Research, Independence Blue Cross Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania. Electronic address:

Dyslipidemia, vascular inflammation, obesity, and insulin resistance often overlap and exacerbate each other. Mutations in low density lipoprotein receptor adaptor protein-1 (LDLRAP1) lead to LDLR malfunction and are associated with the autosomal recessive hypercholesterolemia disorder in humans. However, direct causality on atherogenesis in a defined preclinical model has not been reported. Read More

Am J Pathol 2022 Jul 20;192(7):1028-1052. Epub 2022 Apr 20.

Fukatsu Clinic, Anjo, Japan. Electronic address:

Diabetic nephropathy (DN), once manifested, is unlikely to completely recover. Factors that influence DN progression were explored by investigating the process of glomerulosclerosis and interstitial fibrosis and chronological changes in glucose, albuminuria, hyperfiltration, and expressions of sodium-glucose cotransporter 2 (SGLT2) and hypoxia-inducible factors (HIFs) up to 50 weeks in inducible cAMP early repressor transgenic mice, a model of severe DN. Long-term intervention with the SGLT2 inhibitor canagliflozin or islet transplantation or heminephrectomy was used. Read More

Am J Pathol 2022 Jun 12;192(6):825. Epub 2022 Apr 12.

Am J Pathol 2022 06 4;192(6):887-903. Epub 2022 Apr 4.

Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

Activation of constitutive androstane receptor (CAR) transcription factor by xenobiotics promotes hepatocellular proliferation, promotes hypertrophy without liver injury, and induces drug metabolism genes. Previous work demonstrated that lymphocyte-specific protein-1 (LSP1), an F-actin binding protein and gene involved in human hepatocellular carcinoma, suppresses hepatocellular proliferation after partial hepatectomy. The current study investigated the role of LSP1 in liver enlargement induced by chemical mitogens, a regenerative process independent of tissue loss. Read More