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Uremia Impedes Skeletal Myocyte Myomixer Expression and Fusogenic Activity: Implication for Uremic Sarcopenia Am. J. Pathol. (IF 6.0) Pub Date : 2024-04-17 Takaaki Higashihara, Motoki Odawara, Hiroshi Nishi, Takehito Sugasawa, Yumika Suzuki, Satoshi Kametaka, Reiko Inagi, Masaomi Nangaku
In patients with chronic kidney disease (CKD), skeletal muscle mass and function are known to occasionally decline. However, the muscle regeneration and differentiation process in uremia has not been extensively studied. In mice with CKD induced by adenine-containing diet, the tibialis anterior muscle injured using a barium chloride injection method recovered poorly as compared to control mice. In
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Differentiation of Type 17 Mucosal-Associated Invariant T Cells in Circulation Contributes to the Severity of Sepsis Am. J. Pathol. (IF 6.0) Pub Date : 2024-04-09 Xinying Li, Sicheng Fu, Hao Cheng, Min Ma, Zijian Song, Jun Li, Shuang Wu, Chong Zhang, Xiaoxia Wang, Maoyu Tang, Xuexue Pu, Qiang Ji, Jinquan Liang, Zhibin Zhao, Heinrich Körner, Bin Li, Min Shao, Hua Wang
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Graph Perceiver Network for Lung Tumor and Bronchial Premalignant Lesion Stratification from Histopathology Am. J. Pathol. (IF 6.0) Pub Date : 2024-04-06 Rushin H. Gindra, Yi Zheng, Emily J. Green, Mary E. Reid, Sarah A. Mazzilli, Daniel T. Merrick, Eric J. Burks, Vijaya B. Kolachalama, Jennifer E. Beane
Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous cell carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this context, we present a novel computational approach, the Graph Perceiver Network, leveraging hematoxylin and eosin–stained whole slide images to stratify
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Role of HNF4α-cMyc Interaction in CDE Diet–Induced Liver Injury and Regeneration Am. J. Pathol. (IF 6.0) Pub Date : 2024-04-06 Manasi Kotulkar, Julia Barbee, Diego Paine-Cabrera, Dakota Robarts, Maura O’Neil, Udayan Apte
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Transcription Factor E3/Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Axis in Renal Cell Carcinoma Affects Tumor Microenvironment Am. J. Pathol. (IF 6.0) Pub Date : 2024-04-06 Chung Su Hwang, Yun Kyung Kang, Ji Yun Kim, So Hyun Shin, Joon Young Park, Ji Sun Song, So Young Kim, Se Jin Jung, Jung Hee Lee, Ju-Young Na, Dong Hoon Shin, Jee Yeon Kim, Sung Woo Park, Hyun Jung Lee
The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3
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TGF-β1 Drives Integrin-Dependent Pericyte Migration and Microvascular Destabilization in Fibrotic Disease Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-26 Amanda S. Pellowe, Michelle J. Wu, Tae-Yun Kang, Tracy D. Chung, Adrian Ledesma-Mendoza, Erica Herzog, Andre Levchenko, Ian Odell, John Varga, Anjelica L. Gonzalez
Interactions between endothelial cells (ECs) and mural pericytes (PCs) are critical to maintaining the stability and function of the microvascular wall. Abnormal interactions between these two cell types are a hallmark of progressive fibrotic diseases such as systemic sclerosis (also known as scleroderma). However, the role that PCs play in signaling microvascular dysfunction remains underexplored
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Poorly Differentiated Hepatocellular Carcinoma Cells Avoid Apoptosis by Interacting with T Cells via CD40–CD40L Linkage Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-26 Hanh Vinh Ngo, Thuy Thi Thanh Le, Hieu Ngoc Vu, Hai Hoang, Hiroko Ikenaga, Misako Sato-Matsubara, Sawako Uchida-Kobayashi, Hayato Urushima, Khanh Van Nguyen, Ha Thi Nguyen, Hiroji Shinkawa, Shoji Kubo, Naoko Ohtani, Masaru Enomoto, Akihiro Tamori, Norifumi Kawada
Hepatocellular carcinoma (HCC) was associated with increased soluble CD40 levels in a previous study. This study aimed to investigate CD40's role in liver tumor progression. CD40 levels were examined in HCC patient tissues and various HCC cell lines, and their interaction with CD4T cells was studied. RNA sequencing analysis was performed to explore the mechanisms of CD40 induction. Poorly differentiated
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GLUT1 Promotes NLRP3 Inflammasome Activation of Airway Epithelium in Lipopolysaccharide-Induced Acute Lung Injury Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-26 Jiehong Li, Yijian Li, Guanjin Chen, Yan Liang, Jianpeng Xie, Shuiying Zhang, Kai Zhong, Tong Jiang, Haisu Yi, Haixiong Tang, Xin Chen
Acute lung injury (ALI) is a devastating clinical disease caused by different factors, with high morbidity and mortality. It has been shown that lung injury and inflammation caused by lipopolysaccharide (LPS) can be modulated by NLRP3 inflammasome activation, yet its exact function within the airway epithelium is still unknown. Meanwhile, glucose transporter protein 1 (GLUT1) has been shown to contribute
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Enhanced Optic Nerve Expansion and Altered Ultrastructure of Elastic Fibers Induced by Lysyl Oxidase Inhibition in a Mouse Model of Marfan Syndrome Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-26 Hang-Jing Wu, Evan Krystofiak, John Kuchtey, Rachel W. Kuchtey
Two major constituents of exfoliation material, fibrillin-1 and lysyl oxidase-like 1 (encoded by and ), are implicated in exfoliation glaucoma, yet their individual contributions to ocular phenotype are minor. To test the hypothesis that a combination of mutation and deficiency exacerbates ocular phenotypes, the pan-LOX inhibitor β-aminopropionitrile (BAPN) was used to treat adult wild-type (WT) and
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Cryptochrome 2 Suppresses Epithelial-Mesenchymal Transition by Promoting Trophoblastic Ferroptosis in Unexplained Recurrent Spontaneous Abortion Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-25 Faminzi Li, Liantao Guo, Mengqi Zhou, Lu Han, Shujuan Wu, Lianzhi Wu, Jing Yang
Unexplained recurrent spontaneous abortion (URSA) is a serious reproductive issue that affects women of childbearing age. Studies have shown a close association between disrupted circadian rhythm and impaired epithelial-mesenchymal transition (EMT) process in trophoblasts during URSA, although the underlying mechanism has not been elaborated. This study aims to investigate the regulatory relationship
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Tumor Necrosis Factor Receptor-2 Signals Clear-Cell Renal Carcinoma Proliferation via Phosphorylated 4E Binding Protein-1 and Mitochondrial Gene Translation Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-25 Rafia S. Al-Lamki, Aviva M. Tolkovsky, Mohammad Alawwami, WanHua Lu, Sarah F. Field, Jun Wang, Jordan S. Pober, John R. Bradley
Clear-cell renal cell carcinoma (ccRCC), a tubular epithelial malignancy, secretes tumor necrosis factor (TNF), which signals ccRCC cells in an autocrine manner via two cell surface receptors, TNFR1 and TNFR2, to activate shared and distinct signaling pathways. Selective ligation of TNFR2 was shown to drive cell cycle entry of malignant cells via a signaling pathway involving epithelial tyrosine kinase
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Different Oncogenes and Reproductive Histories Shape the Progression of Distinct Premalignant Clones in Multistage Mouse Breast Cancer Models Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-25 Maryknoll Linscott, Jerry Ruizhe Ren, Shelley Gestl, Edward J. Gunther
A remote carcinogen exposure can predispose to breast cancer onset decades later, suggesting carcinogen-induced mutations generate long-lived premalignant clones. How subsequent events influence the progression of specific premalignant clones remains poorly understood. Here, we generated multistage mouse models of mammary carcinogenesis by combining chemical carcinogen exposure [using 7,12-dimethylbenzanthracene
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Serum Fusion Transcripts to Assess the Risk of Hepatocellular Carcinoma and the Impact of Cancer Treatment through Machine Learning Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-25 Yan-Ping Yu, Silvia Liu, David Geller, Jian-Hua Luo
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A Deep Learning–Based Assessment Pipeline for Intraepithelial and Stromal Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Carcinoma Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-25 Kohei Hamada, Ryusuke Murakami, Akihiko Ueda, Yoko Kashima, Chiho Miyagawa, Mana Taki, Koji Yamanoi, Ken Yamaguchi, Junzo Hamanishi, Sachiko Minamiguchi, Noriomi Matsumura, Masaki Mandai
Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in patients with epithelial ovarian cancer. However, the evaluation of TILs has not been applied to routine clinical practice because of reproducibility issues. We developed two convolutional neural network models to detect TILs and to determine their spatial location in whole slide images, and established a spatial assessment
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Advances in Understanding Cardiovascular Disease Pathogenesis through Next-Generation Technologies Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-20 Cyrine Ben Dhaou, Matthew L. Scott, A. Wayne Orr
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Developmental Dopaminergic Signaling Modulates Neural Circuit Formation and Contributes to Autism Spectrum Disorder–Related Phenotypes Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-16 Xiaojuan Lu, Yixing Song, Jiaqi Wang, Yunyun Cai, Siwan Peng, Jiaqi Lin, Biqin Lai, Junjie Sun, Tianqing Liu, Gang Chen, Lingyan Xing
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Prediction of MET Overexpression in Lung Adenocarcinoma from Hematoxylin and Eosin Images Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-15 Kshitij Ingale, Sun Hae Hong, Josh S.K. Bell, Abbas Rizvi, Amy Welch, Lingdao Sha, Irvin Ho, Kunal Nagpal, Aïcha Bentaieb, Rohan P. Joshi, Martin C. Stumpe
MET protein overexpression is a targetable event in non-small cell lung cancer and is the subject of active drug development. Challenges in identifying patients for these therapies include lack of access to validated testing, such as standardized immunohistochemistry assessment, and consumption of valuable tissue for a single gene/protein assay. Development of prescreening algorithms using routinely
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Sortilin in Biliary Epithelial Cells Promotes Ductular Reaction and Fibrosis during Cholestatic Injury Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-15 Einav Hubel, Anat Neuman, Sigal Fishman, Ortal Schaffer, Noam Erez, Bander Abu Shrkihe, Yuval Shteingard, Tamar Gross, Oren Shibolet, Chen Varol, Isabel Zvibel
Cholestatic injuries are accompanied by ductular reaction, initiated by proliferation and activation of biliary epithelial cells (BECs), leading to fibrosis. Sortilin (encoded by ) facilitates IL-6 secretion and leukemia inhibitory factor (LIF) signaling. This study investigated the interplay between sortilin and IL-6 and LIF in cholestatic injury–induced ductular reaction, morphogenesis of new ducts
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Deletion of MyD88 in T Cells Improves Antitumor Activity in Melanoma Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-03 Abraham L. Bayer, Darwing Padilla-Rolon, Sasha Smolgovsky, Philip Hinds, Pilar Alcaide
Cytotoxic CD8 T cells are central to the antitumor immune response by releasing cytotoxic granules that kill tumor cells. They are activated by antigen-presenting cells, which become activated by DAMPs (damage associated molecular patterns) through MyD88. However, the suppressive tumor microenvironment promotes T-cell tolerance to tumor antigens in part by enhancing the activity of immune checkpoint
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Ficolin-A/2 Aggravated Severe Lung Injury through Neutrophil Extracellular Traps Mediated by Gasdermin D–Induced Pyroptosis Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-03 Li Huang, Xiaowu Tan, Weixia Xuan, Qing Luo, Li Xie, Yunzhu Xi, Rong Li, Li Li, Feifan Li, Meiyun Zhao, Yongliang Jiang, Xu Wu
Neutrophil extracellular traps (NETs) and pyroptosis are critical events in lung injury. This study investigated whether ficolin-A influences NET formation through pyroptosis to exacerbate lipopolysaccharide (LPS)-induced lung injury. The expression of ficolin-A/2, NETs, and pyroptosis-related molecules was investigated in animal and cell models. Knockout and knockdown (recombinant protein) methods
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Tumor Necrosis Factor α–Induced Protein 8–Like Protein 1 Binds to Protein Arginine Methyltransferase 1 To Suppress the Methylation of Signal Transducer and Activator of Transcription 3 and Cell Growth in Oral Squamous Cell Carcinoma Am. J. Pathol. (IF 6.0) Pub Date : 2024-03-02 Bing Liu, Wen Si, Bo Wei, Xuan Zhang, Peng Chen
The tumor necrosis factor α–induced protein 8 (TIPE, also TNFAIP8 or OXi-α) family is a newly discovered series of proteins involved in immune regulation and tumorigenesis. TIPE1, a member of the TIPE/TNFAIP8/OXi-α family, has emerged as an anticancer-drug target, as it is promotes cancer cell apoptosis and inhibits cell proliferation. The current study aimed to systematically reveal that TIPE1 regulates
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The Unrecognized Role of Ninjurin 2 in Inflammation, Metabolism, and Pyroptosis Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-28 Juan Liu, Wenwei Hu, Zhaohui Feng
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Ferroptosis Contributes to Microvascular Dysfunction in Diabetic Retinopathy Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-28 Qun Liu, Chao-Qun Liu, Wan-Zhao Yi, Pei-Wen Ouyang, Bo-Fan Yang, Qi Liu, Jing-Min Liu, Ya-Ni Wu, Ai-Rong Liang, Yu-Hong Cui, Jing Meng, Xiu-Yun Li, Hong-Wei Pan
Ferroptosis is a new form of cell death characterized by iron-dependent lipid peroxidation. Whether ferroptosis is involved in retinal microvascular dysfunction under diabetic condition is not known. The expression of ferroptosis-related genes in patients with proliferative diabetic retinopathy and in diabetic mice was determined with RT-qPCR. Reactive oxygen species, iron content, lipid peroxidation
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Serine Supports Epithelial and Immune Cell Function in Colitis Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-28 Ji Dong K. Bai, Suchandrima Saha, Michael Wood, Bo Chen, Jinyu Li, Lukas E. Dow, David C. Montrose
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract that are largely driven by immune cell activity; mucosal healing is critical for remission. Serine is a nonessential amino acid that supports epithelial and immune cell metabolism and proliferation; however, whether these roles affect IBD pathogenesis is not well understood. Here, we show that serine
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Metallothionein Alleviates Glutathione Depletion-Induced Oxidative Cardiomyopathy through CISD1-Dependent Regulation of Ferroptosis in Murine Hearts Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-28 Feng-Juan Li, Shouzhi Fu, Hua Ye, Yi-Han Hu, Jianxin Chen, Jamie R. Privratsky, Wei Yu, Feng Dong, Russel J. Reiter, Maolong Dong, Jun Guo, Jun Ren
This study was designed to discern the effect of heavy scavenger metallothionein on glutathione (GSH) deprivation-evoked cardiac anomalies and mechanisms involved with an emphasis on ferroptosis. Wild-type and cardiac metallothionein transgenic mice received GSH synthase inhibitor buthionine sulfoximine (BSO; 30 mmol/L in drinking water) for 14 days before assessment of myocardial morphology and function
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Impaired Hepatic Very Low-Density Lipoprotein Secretion Promotes Tumorigenesis and Is Accelerated with Fabp1 Deletion Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-28 Elizabeth P. Newberry, Elizabeth A. Molitor, Allen Liu, Kamyar Chong, Xiuli Liu, Cristina Alonso, Jose M. Mato, Nicholas O. Davidson
Genetic polymorphisms that impair very low-density lipoprotein (VLDL) secretion are linked to hepatic steatosis, fibrosis, and hepatocellular cancer. Liver-specific deletion of microsomal triglyceride transfer protein () impairs VLDL assembly, promoting hepatic steatosis and fibrosis, which are attenuated in null [ double knockout (DKO)] mice. Here, we examine the impact of impaired VLDL secretion
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The Role of miRNA and Long Noncoding RNA in Cholestatic Liver Diseases Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-28 Yudian Zhang, Ying Liu, Wen Huo, Longfei He, Bowen Li, Hui Wang, Fanyin Meng, Chenggang Duan, Bingru Zhou, Jinbo Wu, Rong Chen, Juan Xing, Ying Wan
Cholestatic liver diseases encompass a range of organic damages, metabolic disorders, and dysfunctions within the hepatobiliary system, arising from various pathogenic causes. These factors contribute to disruptions in bile production, secretion, and excretion. Cholestatic liver diseases can be classified into intrahepatic and extrahepatic cholestasis, according to the location of occurrence. The etiology
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Decreased Proteasomal Function Exacerbates Endoplasmic Reticulum Stress-Induced Chronic Inflammation in Obese Adipose Tissue Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-27 Shimpei Nakagawa, Aya Fukui-Miyazaki, Takuma Yoshida, Yasushi Ishii, Eri Murata, Koji Taniguchi, Akihiro Ishizu, Masanori Kasahara, Utano Tomaru
Low-grade chronic inflammation contributes to both aging and the pathogenesis of age-related diseases. White adipose tissue (WAT) in obese individuals exhibits chronic inflammation, which is associated with obesity-related disorders. Aging exacerbates obesity-related inflammation in WAT; however, the molecular mechanisms underlying chronic inflammation and its exacerbation by aging remain unclear.
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REGγ Mitigates Radiation-Induced Enteritis by Preserving Mucin Secretion and Sustaining Microbiome Homeostasis Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-27 Xiangzhan Zhu, Ya Li, Xue Tian, Yiming Jing, Zimeng Wang, Lingling Yue, Jianhui Li, Ling Wu, Xinkui Zhou, Zhidan Yu, Yaodong Zhang, Fangxia Guan, Minglei Yang, Bianhong Zhang
Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is associated closely with gut microbiota dysbiosis. The critical mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. Although the significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating the mucus layer and gut microbiota
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Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-24 Cheryl L. Wang, Jessica M. Skeie, Chantal Allamargot, Andrew S. Goldstein, Darryl Y. Nishimura, James M. Huffman, Benjamin T. Aldrich, Gregory A. Schmidt, Leandro B.C. Teixeira, Markus H. Kuehn, Mark Yorek, Mark A. Greiner
Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluates changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley
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Role of Platelet Activating Factor as a Mediator of Inflammatory Diseases and Preterm Delivery Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-24 Hanan Hamimi Wahid, Fatin Najihah Anahar, Nurul Husna Isahak, Juwairiyah Mohd Zoharodzi, Siti Nur Lina Mohammad Khoiri, Nurul Hayati Mohamad Zainal, Norhidayah Kamarudin, Hamizah Ismail, Mohammed Imad Al-Deen Mustafa Mahmud
Nearly 70% of preterm deliveries occur spontaneously, and the clinical pathways involved include preterm labor and preterm premature rupture of membranes. Prediction of preterm delivery is considered crucial due to the significant effects of preterm birth on health and the economy at both the personal and community levels. Although similar inflammatory processes occur in both term and preterm delivery
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DNA Hypomethylation-Mediated Transcription Dysregulation Participates in Pathogenesis of Polycystic Ovary Syndrome Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-24 Pengbo Cao, Haoran Li, Peijun Wang, Xinna Zhang, Yuxuan Guo, Keyu Zhao, Jiaojiao Guo, Xihe Li, Buhe Nashun
Polycystic ovary syndrome (PCOS) is a highly heterogeneous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidence suggested abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in PCOS. A dehydroepiandrosterone-induced PCOS-like mouse model was generated, which has a similar metabolic and reproductive phenotype
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The Role of Hyaluronan/Receptor for Hyaluronan-Mediated Motility Interactions in the Modulation of Macrophage Polarization and Cartilage Repair Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-24 Emilia Bianchini, Yun Jin Ashley Sin, You Jin Lee, Charles Lin, Utkarsh Anil, Cassie Hamill, Mary K. Cowman, Thorsten Kirsch
Hyaluronan (HA), a negatively charged linear glycosaminoglycan, is a key macromolecular component of the articular cartilage extracellular matrix. The differential effects of HA are determined by a spatially/temporally regulated display of HA receptors, such as CD44 and receptor for hyaluronan-mediated motility (RHAMM). HA signaling through CD44 with RHAMM has been shown to stimulate inflammation and
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Abnormal α-Synuclein Aggregates Cause Synaptic- and Microcircuit-Specific Deficits in the Retinal Rod Pathway Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-21 Tao Xu, Xin Liu, Xin Lin, Jiayi Xiao, Di Zhang, Fenfen Ye, Fan Lu, Jia Qu, Jun Zhang, Jiang-Fan Chen
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A Histopathologic Image Analysis for the Classification of Endocervical Adenocarcinoma Silva Patterns Depend on Weakly Supervised Deep Learning Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-19 Qingqing Liu, Xiaofang Zhang, Xuji Jiang, Chunyan Zhang, Jiamei Li, Xuedong Zhang, Jingyan Yang, Ning Yu, Yongcun Zhu, Jing Liu, Fengxiang Xie, Yawen Li, Yiping Hao, Yuan Feng, Qi Wang, Qun Gao, Wenjing Zhang, Teng Zhang, Taotao Dong, Baoxia Cui
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Ninjurin 2 Modulates Tumorigenesis, Inflammation, and Metabolism via Pyroptosis Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-05 Jin Zhang, Xiangmudong Kong, Hee Jung Yang, Weici Zhang, Mingyi Chen, Xinbin Chen
The nerve injury-induced protein 2 (NINJ2) belongs to a family of homophilic adhesion molecules and was initially found to be involved in nerve regeneration. However, the role of NINJ2 in other cellular processes is not well studied. The -deficient mice generated in the current study had a short lifespan and were prone to spontaneous tumors, systemic inflammation, and metabolic defects. Comprehensive
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Basic Transcription Factor 3 Like 4 Enhances Malignant Phenotypes through Modulating Tumor Cell Function and Immune Microenvironment in Glioma Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-05 Bing Lu, Tianyi Lu, Jiawen Shi, Pingping Sun, Xiaojing Zhang, Lei Yang, Ziheng Wang, Jianfei Huang
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Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-05 Manuela Pizzano, Alexia Vereertbrugghen, Agostina Cernutto, Florencia Sabbione, Irene A. Keitelman, Carolina M. Shiromizu, Douglas Vera Aguilar, Federico Fuentes, Mirta N. Giordano, Analía S. Trevani, Jeremías G. Galletti
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Periostin in Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression by Enhancing Cancer and Stromal Cell Migration Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-05 Shoji Miyako, Yu-ichiro Koma, Takashi Nakanishi, Shuichi Tsukamoto, Keitaro Yamanaka, Nobuaki Ishihara, Yuki Azumi, Satoshi Urakami, Masaki Shimizu, Takayuki Kodama, Mari Nishio, Manabu Shigeoka, Yoshihiro Kakeji, Hiroshi Yokozaki
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are involved in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). CAF-like cells were generated through direct co-culture of human bone marrow–derived mesenchymal stem cells, one of CAF origins, with ESCC cells. Periostin (POSTN) was found to be highly expressed in CAF-like cells. After direct
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Computational Pathology for Prediction of Isocitrate Dehydrogenase Gene Mutation from Whole Slide Images in Adult Patients with Diffuse Glioma Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-05 Yuanshen Zhao, Weiwei Wang, Yuchen Ji, Yang Guo, Jingxian Duan, Xianzhi Liu, Dongming Yan, Dong Liang, Wencai Li, Zhenyu Zhang, Zhi-Cheng Li
Isocitrate dehydrogenase gene () mutation is one of the most important molecular markers of glioma. Accurate detection of status is a crucial step for integrated diagnosis of adult-type diffuse gliomas. Herein, a clustering-based hybrid of a convolutional neural network and a vision transformer deep learning model was developed to detect mutation status from annotation-free hematoxylin and eosin–stained
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WSB1, a Hypoxia-Inducible E3 Ligase, Promotes Myofibroblast Accumulation and Attenuates Alveolar Epithelial Regeneration in Mouse Lung Fibrosis Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-05 Lei Chong, Lihui Zou, Liyan Xiang, Xinyue Song, Wanqi Miao, Xihua Yan, Ming Xu, Gongxia Ling, Elie El Agha, Saverio Bellusci, Zhenkun Lou, Hailin Zhang, Jin-San Zhang
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Model-Agnostic Binary Patch Grouping for Bone Marrow Whole Slide Image Representation Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-05 Youqing Mu, Hamid R. Tizhoosh, Taher Dehkharghanian, Saghir Alfasly, Clinton J.V. Campbell
Histopathology is the reference standard for pathology diagnosis, and has evolved with the digitization of glass slides [ie, whole slide images (WSIs)]. While trained histopathologists are able to diagnose diseases by examining WSIs visually, this process is time consuming and prone to variability. To address these issues, artificial intelligence models are being developed to generate slide-level representations
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Histologic Evidence of Epithelial–Mesenchymal Transition and Autophagy in Human Fetal Membranes Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-04 Mary E. Severino, Lauren S. Richardson, Marian Kacerovsky, Ramkumar Menon
Preterm, prelabor rupture of the human fetal membranes (pPROM) is involved in 40% of spontaneous preterm births worldwide. Cellular-level disturbances and inflammation are effectors of membrane degradation, weakening, and rupture. Maternal risk factors induce oxidative stress (OS), senescence, and senescence-associated inflammation of the fetal membranes as reported mechanisms related to pPROM. Inflammation
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IL-6 Up-Regulates Expression of LIM-Domain Only Protein 4 in Psoriatic Keratinocytes through Activation of the MEK/ERK/NF-κB Pathway Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-04 Zhenzhen Tu, Wei Wei, Fanjun Zeng, Wenwen Wang, Yuyan Zhang, Yintao Zhang, Fusheng Zhou, Chunlin Cai, Siping Zhang, Haisheng Zhou
Psoriasis is a chronic inflammatory skin disease characterized by the activation of keratinocytes and the infiltration of immune cells. Overexpression of the transcription factor LIM-domain only protein 4 (LMO4) promoted by IL-23 has critical roles in regulating the proliferation and differentiation of psoriatic keratinocytes. IL-6, an autocrine cytokine in psoriatic epidermis, is a key mediator of
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Bicellular Localization of Tricellular Junctional Protein Angulin-3/ILDR2 Allows Detection of Podocyte Injury Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-02 Atsuko Y. Higashi, Akira C. Saito, Tomohito Higashi, Kyoko Furuse, Mikio Furuse, Hideki Chiba, Junichiro J. Kazama
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5-Hydroxytryptamine 4 Receptor Agonist Attenuates Diabetic Enteric Neuropathy through Inhibition of the Receptor-Interacting Protein Kinase 3 Pathway Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-02 Yingying Cheng, Yueting Kou, Juan Wang, Yue Wang, Weifang Rong, Hongxiu Han, Guohua Zhang
Necroptosis, considered as a form of programmed cell death, contributes to neural loss. The 5-hydroxytryptamine 4 receptor (5-HTR) is involved in neurogenesis in the enteric nervous system. However, whether the activation of 5-HTR can alleviate diabetic enteric neuropathy by inhibiting receptor-interacting protein kinase 3 (RIPK3)–mediated necroptosis is unclear. This study aimed to explore the beneficial
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Neutrophil Infiltration and Function in the Pathogenesis of Inflammatory Airspace Disease Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-01 Maureen E. Haynes, David P. Sullivan, William A. Muller
Neutrophils are an important cell type often considered the body's first responders to inflammatory insult or damage. They are recruited to the tissue of the lungs in patients with inflammatory airspace diseases and have unique and complex functions that range from helpful to harmful. The uniqueness of these functions is due to the heterogeneity of the inflammatory cascade and retention in the vasculature
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Diabetes Accelerates Steatohepatitis in Mice: Liver Pathology and Single-Cell Gene Expression Signatures Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-01 Tuerdiguli Abuduyimiti, Hisanori Goto, Kumi Kimura, Yu Oshima, Ryota Tanida, Kyoko Kamoshita, Nontaphat Leerach, Halimulati Abuduwaili, Hein Ko Oo, Qifang Li, Cynthia M. Galicia-Medina, Hiroaki Takayama, Kiyo-aki Ishii, Yujiro Nakano, Yumie Takeshita, Tomohiro Iba, Hisamichi Naito, Masao Honda, Kenichi Harada, Yasuhiko Yamamoto, Toshinari Takamura
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PDGF-D Is Dispensable for the Development and Progression of Murine Alport Syndrome Am. J. Pathol. (IF 6.0) Pub Date : 2024-02-01 Emilia Anouk Margo Firat, Eva Miriam Buhl, Nassim Bouteldja, Bart Smeets, Ulf Eriksson, Peter Boor, Barbara Mara Klinkhammer
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Omics Approaches Unveiling the Biology of Human Atherosclerotic Plaques Am. J. Pathol. (IF 6.0) Pub Date : 2024-01-25 Xun Wu, Hanrui Zhang
Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the buildup of plaques with the accumulation and transformation of lipids, immune cells, vascular smooth muscle cells, and necrotic cell debris. Plaques with collagen-poor thin fibrous caps infiltrated by macrophages and lymphocytes are considered unstable because they are at the greatest risk of rupture and clinical
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Chronic Sleep Deprivation Impairs Visual Functions via Oxidative Damage in Mice Am. J. Pathol. (IF 6.0) Pub Date : 2024-01-18 Liying Tang, Houjian Zhang, Yi Liao, Shengmei Zhou, Yaqiong Yang, Mouxin Zhang, Yuli Guo, Tingyu Xie, Shikun Chen, Weijie Ouyang, Xiang Lin, Shaopan Wang, Caihong Huang, Minjie Zhang, Jingbin Zhuang, Jiankai Zhao, Rongrong Zhang, Changjun Zhang, Zibing Jin, Jiaoyue Hu, Zuguo Liu
Sleep deprivation (SD) is a global public health burden, and has a detrimental role in the nervous system. Retina is an important part of the central nervous system; however, whether SD affects retinal structures and functions remains largely unknown. Herein, chronic SD mouse model indicated that loss of sleep for 4 months could result in reductions in the visual functions, but without obvious morphologic
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IL-22 Binding Protein/IL-22 Axis in Regulating Acute Lung Injury Am. J. Pathol. (IF 6.0) Pub Date : 2024-01-08 Amber Pillar, Md Khadem Ali
Abstract not available
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Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease Am. J. Pathol. (IF 6.0) Pub Date : 2024-01-01 Sumit Kumar Anand, Theresea-Anne Governale, Xiangyu Zhang, Babak Razani, Arif Yurdagul Jr., Christopher B. Pattillo, Oren Rom
Despite significant advances in medical treatments and drug development, atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death worldwide. Dysregulated lipid metabolism is a well-established driver of ASCVD. Unfortunately, even with potent lipid-lowering therapies, ASCVD-related deaths have continued to increase over the past decade, highlighting an incomplete understanding