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Am J Pathol 2019 Apr 12. Epub 2019 Apr 12.

This commentary highlights the article by Li et al that identified the centrosomal protein CEP 72 as a biomarker for prognosis of urothelial cancer. Read More

Am J Pathol 2019 Apr 12. Epub 2019 Apr 12.

Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address:

This commentary highlights the article by Fang et al that describes the role of EZH2 in endometrial development. Read More

Am J Pathol 2019 Apr 12. Epub 2019 Apr 12.

Am J Pathol 2019 Apr 10. Epub 2019 Apr 10.

Department of Plastic and Reconstructive Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. Electronic address:

Wound healing is a process of cutaneous barrier reconstruction that occurs after skin injury and involves diverse cytokines and cell types. Similar to several deubiquitinating enzymes, ubiquitin-specific peptidase 15 (USP15) can remove ubiquitin chains from specific proteins to rescue them from degradation. However, the regulatory role of USP15 in wound healing remains unclear. Read More

Am J Pathol 2019 Apr 10. Epub 2019 Apr 10.

Department of Psychology and Neuroscience; Department of Psychiatry; Department of Pathology; Brain Repair Centre, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address:

Pathological inflammation in response to injury, infection, or oxidative stress is a proposed mechanism relating cognitive decline to dementia. The kynurenine pathway and thioredoxin-interacting protein (TXNIP) activity regulate inflammation and neurotoxicity in Alzheimer disease (AD). We examined cognitive deficits, kynurenine pathway mediators, TXNIP, and oxidative damage in the cerebrum and spleen, as well as inflammatory cytokine production by stimulated splenocytes, from female 3xTg-AD mice in early and late stages of disease progression. Read More

Am J Pathol 2019 Apr 4. Epub 2019 Apr 4.

Department of Medicine, Mayo Clinic, Scottsdale, AZ. Electronic address:

Acute lipolysis of visceral fat or circulating triglycerides may worsen acute pancreatitis-associated local and systemic injury. The pancreas expresses pancreatic triacylglycerol lipase (PNLIP), pancreatic lipase related protein 2 (PNLIPRP2), and carboxyl ester lipase (CEL), which may leak into the visceral fat or systemic circulation during pancreatitis. We thus aimed to determine the pancreatic lipase(s) regulating lipotoxicity during acute pancreatitis. Read More

Am J Pathol 2019 Apr 5. Epub 2019 Apr 5.

Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas. Electronic address:

Normal proliferation and differentiation of uterine epithelial cells are critical for uterine development and function. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), a core component of polycomb repressive complexes 2, possesses histone methyltransferase activity that catalyzes the trimethylation of lysine 27 of histone H3. EZH2 has been involved in epithelial-mesenchymal transition, a key event in development and carcinogenesis. Read More

Am J Pathol 2019 Apr 4. Epub 2019 Apr 4.

Inserm UMR U1069, Tours, France;; Department of Pathology, CHU-Universite de Tours, 37000 Tours, France;. Electronic address:

In prostate cancer research, there is a lack of valuable preclinical models. Tumor cell heterogeneity and sensitivity to microenvironment signals, such as hypoxia or extracellular calcium concentration, are difficult to reproduce. Here, we developed and characterized an ex vivo tissue culture model preserving these properties. Read More

Am J Pathol 2019 Apr 4. Epub 2019 Apr 4.

Baylor Scott & White Digestive Disease Research Center, Temple, Texas; Division of Research, Central Texas Veterans Health Care System, Temple, Texas. Electronic address:

Hepatitis C virus (HCV) infection is a global public health problem because it is a main cause of liver cirrhosis and hepatocellular carcinoma. This human oncogenic virus is also associated with the development of non-Hodgkin lymphoma and cholangiocarcinoma (CCA). The association between HCV infection and CCA has been examined in a number of epidemiologic studies. Read More

Am J Pathol 2019 Apr 3. Epub 2019 Apr 3.

State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

A vital constituent of the centrosome involved in regulating the activity of the organelle during the cell cycle is Centrosomal protein 72 (CEP72), whose function in the case of human cancer yet lacks clarity. Expression dynamics of CEP72 and its clinical impact were examined in a large cohort of bladder tissues. Several experiments at both in vitro and in vivo levels on urothelial carcinoma of the bladder (UCB) cells were conducted to understand the role of this molecule along with the mechanisms. Read More

Am J Pathol 2019 Mar 27. Epub 2019 Mar 27.

Department of Pathology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA. Electronic address:

The liver contains diploid and polyploid hepatocytes (tetraploid, octaploid, etc.), with polyploids comprising ≥90% of the hepatocyte population in adult mice. Polyploid hepatocytes form multipolar spindles in mitosis, which lead to chromosome gains/losses and random aneuploidy. Read More

Am J Pathol 2019 Mar 26. Epub 2019 Mar 26.

Department of Neurological Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.

Six subgroups of sporadic Creutzfeldt-Jakob disease have been identified by distinctive clinicopathological features, genotype at polymorphic codon 129 (methionine/valine, M/V) of the PRNP gene, and type of abnormal prion proteins (type 1 or 2). In addition to the pure subgroups, mixed neuropathological features and co-existence of two types of abnormal prion proteins in the same patient have also been reported. Here, we found that a portion of the patients previously diagnosed as MM1 had neuropathological characteristics of MM2 thalamic form, ie, neuronal loss of the inferior olivary nucleus of the medulla. Read More

Am J Pathol 2019 Mar 26. Epub 2019 Mar 26.

Department of Medicine, Division of Nephrology, University of Louisville, Louisville, KY;; Robley Rex VA Medical Center, Louisville, KY. Electronic address:

The Na/H exchange regulatory factor 1 (NHERF1) is a scaffolding protein that anchors multiple membrane proteins in renal proximal tubules. Cultured proximal tubule cells deficient in NHERF1 and proximal tubules from NHERF1 deficient mice exhibit aberrant trafficking. NHERF1 deficient cells also exhibit altered transcription pattern and worse survival. Read More

Am J Pathol 2019 Mar 26. Epub 2019 Mar 26.

Pulmonary Critical Care and Sleep Medicine, Department of Internal Medicine, Rush Medical College, Chicago, Illinois. Electronic address:

As time progresses, our understanding of disease pathology is propelled forward by technological advancements. Much of the advancements that aid in understanding disease mechanics are based on animal studies. Unfortunately, animal models often fail to recapitulate the entirety of the human disease. Read More

Am J Pathol 2019 Mar 26. Epub 2019 Mar 26.

INSERM UMR_S 999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Hôpital Marie Lannelongue, Le Plessis-Robinson, France; University Paris-Sud, Faculté de Médecine, Université Paris-Saclay, AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire, Hôpital Bicêtre, Le Kremlin Bicêtre, France. Electronic address:

Hepatic veno-occlusive disease (HVOD), alias sinusoidal obstruction syndrome, may develop as a complication of chemotherapy in the setting of hematopoietic stem cell transplantation. HVOD is less frequently described after exposure to chemotherapy in the nontransplant setting and can also be a complication after ingestion of toxins, such as pyrrolizidine alkaloids. Veno-occlusive disease may also affect the lungs, and it is therefore termed pulmonary veno-occlusive disease (PVOD). Read More

Am J Pathol 2019 Mar 27. Epub 2019 Mar 27.

Department of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; George M. O'Brien Research Center of Excellence, University of Wisconsin, Madison, Wisconsin; Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin. Electronic address:

Survival rates decrease significantly when localized prostate cancer (CaP) becomes metastatic, emphasizing the need for improved targeted therapies. DDX3, an RNA helicase, has widespread functions in RNA regulation, in both the nucleus and cytoplasm. Although DDX3 has been implicated as a prognostic marker for many cancers, including primary CaP, its expression, localization, and function in metastatic CaP have not been investigated. Read More

Am J Pathol 2019 Mar 27. Epub 2019 Mar 27.

Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada.

Monocyte lineage cells play important roles in health and disease. Their differentiation into macrophages is crucial for a broad array of immunologic processes that regulate inflammation, neoplasia, and infection. In certain pathologic conditions, such as foreign body reactions and peripheral inflammatory lesions, monocytes fuse to form large, multinucleated giant cells (MGCs). Read More

Am J Pathol 2019 Mar 27. Epub 2019 Mar 27.

Department of Biomedicine, Aarhus University, Aarhus, Denmark. Electronic address:

Severe urinary tract infections are commonly caused by sub-strains of Escherichia coli secreting the pore-forming virulence factor α-hemolysin (HlyA). Repeated or severe cases of pyelonephritis can cause renal scarring that subsequently can lead to progressive failure. We have previously demonstrated that HlyA releases cellular ATP directly through its membrane pore and that acute HlyA-induced cell damage is completely prevented by blocking ATP signaling. Read More

Am J Pathol 2019 Apr;189(4):706-718

Department of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana. Electronic address:

Sickle cell disease (SCD) is one of the most common hereditary hemoglobinopathies worldwide, affecting almost 400,000 newborns globally each year. It is characterized by chronic hemolytic anemia and endothelial dysfunction, resulting in a constant state of disruption of the vascular system and leading to recurrent episodes of ischemia-reperfusion injury (I/RI) to multiple organ systems. I/RI is a fundamental vascular pathobiological paradigm and contributes to morbidity and mortality in a wide range of conditions, including myocardial infarction, stroke, acute kidney injury, and transplantation. Read More

Am J Pathol 2019 Mar 19. Epub 2019 Mar 19.

The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology. Read More

Am J Pathol 2019 Mar 18. Epub 2019 Mar 18.

Division of Pulmonary-Critical Care, Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Pathology, Duke University Medical Center, Durham, North Carolina. Electronic address:

Radiation-induced pulmonary fibrosis (RTPF) is a progressive, serious condition in many subjects treated for thoracic malignancies or after accidental nuclear exposure. No biomarker exists for identifying the irradiated subjects most susceptible to pulmonary fibrosis (PF). Previously, we determined that gastrin-releasing peptide (GRP) was elevated within days after birth in newborns exposed to hyperoxia who later developed chronic lung disease. Read More

Am J Pathol 2019 Apr 13;189(4):924-939. Epub 2019 Mar 13.

Division of Lymphatic Biology, Department of Medical Physiology, Texas A&M College of Medicine, College Station. Electronic address:

Obese adipose tissue expansion is an inflammatory process that results in dysregulated lipolysis, increased circulating lipids, ectopic lipid deposition, and systemic insulin resistance. Lymphatic vessels provide a route of fluid, macromolecule, and immune cell clearance, and lymphangiogenesis increases this capability. Indeed, inflammation-associated lymphangiogenesis is critical in resolving acute and chronic inflammation, but it is largely absent in obese adipose tissue. Read More

Am J Pathol 2019 Mar 9. Epub 2019 Mar 9.

Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China. Electronic address:

Mitochondrial ribosome proteins (MRPs), which are encoded by the nuclear genomic DNA, are important for mitochondrial-encoded protein synthesis and mitochondrial function. Emerging evidence suggests that several MRPs also exhibit important extra-mitochondrial functions, such as involvement in apoptosis, protein biosynthesis, and signal transduction. In this study, we demonstrate a significant role of MRP L35 (MRPL35) in colorectal cancer (CRC). Read More

Am J Pathol 2019 Mar;189(3):699-700

Am J Pathol 2019 Mar;189(3):492-501

Department of Pathology and Biochemistry, Weill Cornell Medicine, Cornell University, New York. Electronic address:

The complex relationship between diet and metabolism is an important contributor to cellular metabolism and health. Over the past few decades, a central role for mammalian target of rapamycin (mTOR) in the regulation of multiple cellular processes, including the response to food intake, maintaining homeostasis, and the pathogenesis of disease, has been shown. Herein, we first review our current understanding of the biochemical functions of mTOR and its response to fluctuations in hormone levels, like insulin. Read More

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

Department of Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania; St. Christopher's Hospital for Children, Philadelphia, Pennsylvania. Electronic address:

Bronchopulmonary dysplasia (BPD) is a disease prevalent in preterm babies with a need for supplemental oxygen, resulting in impaired lung development and dysregulated vascularization. Epidemiologic studies have shown that males are more prone to BPD and have a delayed recovery compared with females, for reasons unknown. Herein, we tried to recapitulate mild, moderate, and severe BPD, using two different strains of mice, in males and females: CD1 (outbred) and C57BL/6 (inbred). Read More

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

Department of Gynecology, Shiyan Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, China. Electronic address:

Hepatoblastoma (HB), the most common pediatric primary liver neoplasm, shows nuclear localization of β-catenin and yes-associated protein 1 (YAP1) in almost 80% of the cases. Coexpression of constitutively active S127A-YAP1 and ΔN90 deletion-mutant β-catenin (YAP1-ΔN90-β-catenin) causes HB in mice. Because heterogeneity in downstream signaling is being identified owing to mutational differences even in the β-catenin gene alone, we investigated if co-expression of point mutants of β-catenin (S33Y or S45Y) with S127A-YAP1 led to similar tumors as YAP1-ΔN90-β-catenin. Read More

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, Rome, Italy.

Cystinosis is a rare lysosomal storage disorder caused by loss-of-function mutations of the CTNS gene, encoding cystinosin, a symporter that mediates cystine efflux from lysosomes. Approximately 95% of patients with cystinosis display renal Fanconi syndrome, short stature, osteopenia, and rickets. In this study, we investigated whether the absence of cystinosin primarily affects bone remodeling activity, apart from the influences of the Fanconi syndrome on bone mineral metabolism. Read More

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, San Francisco, California. Electronic address:

Hepatoblastoma (HB) is the most common type of pediatric liver cancer. Activation of yes-associated protein (YAP) has been implicated in HB molecular pathogenesis. The transcriptional co-activator Yap regulates downstream gene expression through interaction with the TEA domain (TEAD) proteins. Read More

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Drum Tower Hospital, Model Animal Research Center, Nanjing University, Nanjing, China. Electronic address:

Missense mutations in the gasdermin-A3 (Gsdma3) gene are associated with skin inflammation and hair loss in mice. However, the physiological function of Gsdma3 remains unclear. Herein, we reported that mice carrying the Gsdma3 Y344H mutation that encodes a presumptive activated form of Gsdma3 show increased heat production along with lower body fat percentages. Read More

Am J Pathol 2019 Feb 18. Epub 2019 Feb 18.

Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Recent technical improvements in both mass spectrometry and protein extraction have made it possible to use formalin-fixed, paraffin-embedded (FFPE) tissues for proteome analysis. In this study, comparable proteome analysis of FFPE tissues revealed multiple candidate marker molecules for differentiating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) from lipoma. A total of 181 unique proteins were identified for ALT/WDL. Read More

Am J Pathol 2019 Apr 13;189(4):705. Epub 2019 Feb 13.

The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology. Read More

Am J Pathol 2019 Mar 12;189(3):619-631. Epub 2019 Feb 12.

Department of Biophysics, Ruhr University Bochum, Bochum, Germany. Electronic address:

Histopathological differentiation between severe urocystitis with reactive urothelial atypia and carcinoma in situ (CIS) can be difficult, particularly after a treatment that deliberately induces an inflammatory reaction, such as intravesical instillation of Bacillus Calmette-Guèrin. However, precise grading in bladder cancer is critical for therapeutic decision making and thus requires reliable immunohistochemical biomarkers. Herein, an exemplary potential biomarker in bladder cancer was identified by the novel approach of Fourier transform infrared imaging for label-free tissue annotation of tissue thin sections. Read More

Am J Pathol 2019 Feb 5. Epub 2019 Feb 5.

Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, People's Republic of China; Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, People's Republic of China; Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, People's Republic of China. Electronic address:

It has been reported that disorders of epigenetic modulation play a critical role in carcinogenesis. Methyl-CpG binding domain protein 2 (MBD2) is known to act as an epigenetic modulator in various types of tumors; however, the role of MBD2 in lung adenocarcinoma (LUAD) remains unclear. Herein, we demonstrated the down-regulation of MBD2 in LUAD compared with adjacent nontumor tissues. Read More

Am J Pathol 2019 Feb 6. Epub 2019 Feb 6.

Department of Medicine, University of Tennessee Medical Center, Knoxville, Tennessee. Electronic address:

Light chain-associated amyloidosis is characterized by the extracellular deposition of amyloid fibrils in abdominothoracic organs, skin, soft tissue, and peripheral nerves. Phagocytic cells of the innate immune system appear to be ineffective at clearing the material; however, human light chain amyloid extract, injected subcutaneously into mice, is rapidly cleared in a process that requires neutrophil activity. To better elucidate the phagocytosis of light chain fibrils, a potential method of cell-mediated dissolution, amyloid-like fibrils were labeled with the pH-sensitive dye pHrodo red and a near infrared fluorophore. Read More

Am J Pathol 2019 Apr 31;189(4):762-772. Epub 2019 Jan 31.

Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address:

Increased angiogenesis is a characteristic feature of remodeling in asthmatic airways and stems from the imbalance between pro-angiogenic and anti-angiogenic factors. Surprisingly, the factors regulating this process in allergic asthma are poorly defined. Previously, we showed an important role of semaphorins 3E (Sema3E) in growth factor-induced airway smooth muscle proliferation and migration in vitro, and in down-regulating airway inflammation, T helper 2/T helper 17 cytokine response, mucus cell hyperplasia, and airway hyperresponsiveness in vivo. Read More

Am J Pathol 2019 Apr 1;189(4):797-812. Epub 2019 Feb 1.

Department of Medicine, Pennsylvania State University, School of Medicine, Hershey, Pennsylvania; Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico. Electronic address:

Lipopolysaccharides (LPSs) are a major component of Gram-negative bacterial cell wall and play an important role in promoting intestinal inflammatory responses. Recent studies have shown that physiologically relevant concentrations of LPS (0 to 2000 pg/mL) cause an increase in intestinal epithelial tight junction (TJ) permeability without causing cell death. However, the intracellular pathways and the mechanisms that mediate LPS-induced increase in intestinal TJ permeability remain unclear. Read More

Am J Pathol 2019 Apr 1;189(4):826-838. Epub 2019 Feb 1.

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Single-nucleotide polymorphisms and rare mutations in factor H (FH; official name, CFH) are associated with age-related macular degeneration and atypical hemolytic uremic syndrome, a form of thrombotic microangiopathy. Mice with the FH W1206R mutation (FH) share features with human atypical hemolytic uremic syndrome. Herein, we report that FH mice exhibited retinal vascular occlusion and ischemia. Read More

Am J Pathol 2019 Apr 30;189(4):847-867. Epub 2019 Jan 30.

Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania; Division of Urology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Caveolins (CAVs) are structural proteins of caveolae that function as signaling platforms to regulate smooth muscle contraction. Loss of CAV protein expression is associated with impaired contraction in obstruction-induced bladder smooth muscle (BSM) hypertrophy. In this study, microarray analysis of bladder RNA revealed down-regulation of CAV1, CAV2, and CAV3 gene transcription in BSM from models of obstructive bladder disease in mice and humans. Read More

Am J Pathol 2019 Apr 29;189(4):784-796. Epub 2019 Jan 29.

Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan; Department of Surgical Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan; Department of Histopathology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address:

Liver metastasis is a major cause of death in patients with gastric cancer. The molecular alterations in clinically resected liver metastases of gastric cancer were evaluated to identify candidate biomarkers and therapeutic targets. Seventy-four patients, including 37 with liver metastasis who underwent gastrectomy and hepatectomy for gastric cancer and 37 without liver metastasis who underwent gastrectomy for gastric cancer, were studied. Read More

Am J Pathol 2019 Apr 29;189(4):911-923. Epub 2019 Jan 29.

Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago. Electronic address:

A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium. Read More

Am J Pathol 2019 Apr 22;189(4):739-752. Epub 2019 Jan 22.

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, People's Republic of China. Electronic address:

This study aimed to identify potential biomarkers for primary open-angle glaucoma (POAG) diagnosis. First, long noncoding RNA (lncRNA) and mRNA expression profiles in the aqueous humor (AH) from 10 POAG and 10 control patients were accessed by microarray analyses. Coding-noncoding gene coexpression networks were drawn to predict potential lncRNA functions. Read More

Am J Pathol 2019 Apr 21;189(4):839-846. Epub 2019 Jan 21.

Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan. Electronic address:

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the production of ANCAs and systemic necrotizing vasculitis in small vessels. Disordered regulation of neutrophil extracellular traps (NETs) is critically involved in the pathogenesis of AAV. NETs are web-like DNA decorated with antimicrobial proteins; they are extruded from activated neutrophils. Read More

Am J Pathol 2019 Feb;189(2):479

Am J Pathol 2019 Feb;189(2):229-230

Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas. Electronic address:

This commentary highlights the article by Hathaway-Schrader et al that studies the impact of antibiotic-disruption of the gut microbiota on long-term bone development. Read More

Am J Pathol 2019 Apr 19;189(4):886-899. Epub 2019 Jan 19.

State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. Electronic address:

Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in the periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown. Read More

Am J Pathol 2019 Apr 19;189(4):753-761. Epub 2019 Jan 19.

Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, United Kingdom. Electronic address:

Glucocorticoid-induced secondary osteoporosis is the most predictable side effect of this anti-inflammatory. One of the main mechanisms by which glucocorticoids achieve such deleterious outcome in bone is by antagonizing Wnt/β-catenin signaling. Sclerostin, encoded by Sost gene, is the main negative regulator of the proformative and antiresorptive role of the Wnt signaling pathway in the skeleton. Read More

Am J Pathol 2019 Apr 19;189(4):868-885. Epub 2019 Jan 19.

Division of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address:

Mitogen-activated protein kinases, including c-Jun NH2-terminal kinase (JNK), play an important role in the development and function of a large variety of tissues. The skeletal phenotype of JNK1 and JNK2 double-knockout (dKO) mice (JNK1Col2-Cre/JNK2) and control genotypes were analyzed at different embryonic and postnatal stages. JNK1/2 dKO mice displayed a severe scoliotic phenotype beginning during development that was grossly apparent around weaning age. Read More

Am J Pathol 2019 Apr 19;189(4):773-783. Epub 2019 Jan 19.

Department of Pathology, Wakayama Medical University School of Medicine, Wakayama, Japan.

Smad3 has circadian expression; however, whether Smad3 affects the expression of clock genes is poorly understood. Here, we investigated the regulatory mechanisms between Smad3 and the clock genes Dec1, Dec2, and Per1. In Smad3 knockout mice, the amplitude of locomotor activity was decreased, and Dec1 expression was decreased in the suprachiasmatic nucleus, liver, kidney, and tongue compared with control mice. Read More

Am J Pathol 2019 Feb 16;189(2):370-390. Epub 2019 Jan 16.

Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, South Carolina; Endocrinology Division, Department of Pediatrics, Medical University of South Carolina College of Medicine, Charleston, South Carolina. Electronic address:

Commensal gut microbiota-host immune responses are experimentally delineated via gnotobiotic animal models or alternatively by antibiotic perturbation of gut microbiota. Osteoimmunology investigations in germ-free mice, revealing that gut microbiota immunomodulatory actions critically regulate physiologic skeletal development, highlight that antibiotic perturbation of gut microbiota may dysregulate normal osteoimmunological processes. We investigated the impact of antibiotic disruption of gut microbiota on osteoimmune response effects in postpubertal skeletal development. Read More