AMERICAN JOURNAL OF PATHOLOGY美国病理学杂志
AMERICAN JOURNAL OF PATHOLOGY(英文缩写 AM J PATHOL),ISSN 0002-9440,eISSN 1525-2191,中文译名:美国病理学杂志 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 5.770 | Q1 |
| 2022 | 6.000 | Q1 |
| 2023 | 4.700 | Q1 |
| 2024 | 3.600 | Q1 |
| 2025 | 4.900 | Q1 |
AMERICAN JOURNAL OF PATHOLOGY 最新收录文献
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1. Multi-Omic Analysis of Peripheral Circulating Neutrophils and the Effects of Transmigration.
1. 外周循环中性粒细胞的多组分分析和迁移的影响PMID:日期:2026-10-03Neutrophils, the most prevalent leukocytes in circulation, are integral to initiating and resolving inflammatory responses. While traditionally viewed as a homogeneous population, emerging studies have revealed significant phenotypic heterogeneity and functional versatility within the neutrophil population. However, developing a consensus on neutrophil markers for precise and comprehensive identification of neutrophil phenotypes at baseline is essential to deepen our understanding of their biology. In this study, we employed a combination of single-cell RNA sequencing (scRNA-seq) and advanced multiplex flow cytometry analyses to examine the transcriptional and proteomic landscapes of human neutrophils in healthy peripheral blood while employing functional assays to assess their migratory capabilities and phenotypic alterations post-transmigration. Through transcriptional and proteomic analyses, our findings identify three distinct neutrophil profiles, each characterized by specific effector functions and migratory patterns. These subsets demonstrated distinction in the expression of markers related to neutrophil maturation, aging, immune modulation, and inflammatory responses, suggesting a complex spectrum of neutrophil states in circulation and post-vascular transmigration. Our findings advance the field's understanding of neutrophil heterogeneity and offer a more nuanced view of their roles in homeostasis and the immune response.
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2. TGF-β3-mediated suppression of SOX2 and OCT4 drives a predominantly non-canonical profile of epithelial-mesenchymal transition during palatal fusion.
2. TGF-β3介导的SOX2和OCT4抑制驱动腭融合过程中以上皮-间充质非经典特征为主的转变PMID:日期:2026-09-22Epithelial-mesenchymal transition (EMT) of medial edge epithelial cells is a critical mechanism underlying embryonic palatal fusion, driven by transforming growth factor beta 3 (TGF-β3). However, its regulatory interplay with pluripotency factors (SOX2/OCT4) and reliance on downstream cascades remain poorly understood. This study investigates these networks to elucidate the mechanisms of cellular reprogramming during palatogenesis. Embryonic day 15 C57BL6/J mouse palatal epithelial cells were isolated to eliminate mesenchymal interference. Cells were subjected to recombinant TGF-β3 (1, 3, 10 ng/mL) or targeted siRNA knockdowns of Tgfb3, Sox2, Oct4, and Smad2/3, and evaluated via RNA sequencing, qRT-PCR, immunofluorescence, TEER, and flow cytometry. Treatment with 1-3 ng/mL TGF-β3 successfully induced EMT in vitro, characterized by decreased E-cadherin, increased fibronectin, diminished membrane resistance, and a fibroblast-like morphological shift. This transition was predominantly associated with non-canonical pathways; phosphorylated Smad2/3 levels remained unchanged while Smad-independent mediators (p38 MAPK and Mmp13) were upregulated (p<0.05). Furthermore, TGF-β3 downregulated the pluripotency markers Sox2 and Oct4 (p<0.05). Combined Sox2/Oct4 knockdown with TGF-β3 yielded the most pronounced EMT characteristic. While Tgfb3 knockdown heavily attenuated EMT, partial mesenchymal transition persisted, indicating redundant compensatory networks. In conclusion, optimal TGF-β3 concentrations (1-3 ng/mL) shift EMT toward Smad-independent pathways during palatogenesis. This reprogramming requires TGF-β3 to suppress SOX2 and OCT4, underscoring their roles as negative regulators of EMT during palatal fusion.
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3. TAK1 Impedes Peripheral Nerve Regeneration After Injury by Evoking Sustained Inflammation.
PMID:日期:2026-09-22Peripheral nerve injury (PNI) often leads to severe functional deficits, yet the molecular mechanisms underlying nerve regeneration remain incompletely understood. Here, the function of transforming growth factor-β-activated kinase 1 (TAK1) in peripheral nerve regeneration was examined using murine and rat models of sciatic nerve injury. The results show that TAK1 overexpression impairs nerve regeneration and functional recovery, whereas pharmacological inhibition of TAK1 with Takinib promotes these processes. Mechanistically, the detrimental effects of TAK1 are associated with sustained inflammatory responses within the sciatic nerve. TAK1 is predominantly expressed in Schwann cells and fibroblasts in the sciatic nerve, where it activates NF-κB signaling. Specifically, TAK1 phosphorylates protein phosphatase 1 regulatory subunit 18 (PPP1R18) at serine 213, thereby relieving its suppression on the NF-κB pathway and facilitating the nuclear accumulation of NF-κB p65. This activation drives chemokine expression, leading to enhanced recruitment of M1 macrophages and the establishment of a proinflammatory microenvironment that impedes remyelination and nerve regeneration. Collectively, these findings identify TAK1 as a critical negative regulator of peripheral nerve repair and highlight TAK1 inhibition as a potential therapeutic approach for improving recovery following PNI.
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4. Complement Factor B Blockade by Iptacopan Drives Antitumor Complement-Based Immunomodulation in Pancreatic Cancer Microenvironment.
PMID:日期:2026-09-22Recent advanced comprehensive analyses reveal complement factors as critical regulators of cancer-immune system interactions. It was previously identified that complement factor B (CFB), a key secreted component of the alternative complement pathway, is aberrantly up-regulated in pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor progression. Iptacopan (LNP023), a selective CFB inhibitor, has established efficacy in complement-mediated disorders; however, its anticancer potential remains unexplored. The effects of iptacopan on PDAC cell biology and the tumor immune microenvironment were investigated using in vitro assays and orthotopic mouse models. Iptacopan significantly suppressed human and murine PDAC cell proliferation and enhanced gemcitabine cytotoxicity. Mechanistically, CFB inhibition induced senescence, as evidenced by increased senescence-associated β-galactosidase activity and p21 up-regulation. In in vivo preclinical studies, iptacopan reduced tumor growth, diminished intratumoral CFB and C5b-9 deposition, and increased p21 expression, indicating tumor-localized complement inhibition. Furthermore, iptacopan decreased conventional Foxp3 regulatory T cells and the immunosuppressive CD8/Foxp3 regulatory T-cell subset while enhancing CD8 tumor-infiltrating lymphocytes, reshaping the tumor immune microenvironment. Combination therapy with immune checkpoint blockades (anti-programmed death-1 and anti-cytotoxic T-lymphocyte-associated protein 4) further augmented antitumor effects, and triple therapy with gemcitabine/nab-paclitaxel yielded the greatest tumor suppression. These results show that iptacopan exerts dual antitumor effects by inducing tumor-intrinsic senescence and promoting an immunostimulatory tumor immune microenvironment. CFB inhibition therefore represents a promising complement-based immunomodulatory treatment for PDAC.
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5. Pathobiology, Mechanisms, and Innovations in Ocular Disease.
5. 眼部疾病的病理生物学、机制和创新PMID:日期:2026-09-21该文献暂无摘要。
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6. Immunologically Active Cardiac Fibroblasts expressing MHC-II promote Doxorubicin cardiotoxicity.
6. 表达MHC-II的免疫活性心脏成纤维细胞促进多柔比星心脏毒性PMID:日期:2026-09-21A common side effect of the chemotherapeutic anthracycline, doxorubicin, is cardiotoxicity and progression to heart failure. Patients treated with anthracyclines show increased circulating cytotoxic CD8IFN-γ T cells. In mice, cumulative doses of doxorubicin also result in increased circulating and cardiac infiltrating CD8IFN-γ T cells, and these cells are required for pathological fibrosis and contractile dysfunction. The present study demonstrates that cardiac fibroblasts become immunologically active and express major histocompatibility complex (MHC) class II on the onset of doxorubicin cardiotoxicity in humans and in mice. Using adoptive transfer and in vitro mechanistic studies, the results show that CD8IFN-γ T cells are required for cardiac fibroblast expression of MHC-II in mice treated with doxorubicin, and that doxorubicin induces cardiac fibroblast expression of CXCL9, resulting in CD8IFN-γ T cell cardiotropism. Selective deletion of MHC-II in cardiac fibroblasts ameliorates systolic dysfunction and dampens cardiac fibrosis induced by doxorubicin in mice. Mechanistically, this study shows that cardiac fibroblast MHC-II is required for cardiac CD4IFN-γ T cell infiltration and proliferation, necessary for cardiac CD8 T cell immune responses and cytotoxicity. These results position cardiac fibroblast MHC-II as a key mediator of contractile dysfunction in doxorubicin cardiotoxicity.
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7. Establishment of a Colorectal Cancer Liver Metastasis Solitary Tumor Mouse Model.
7. 大肠癌癌症肝转移孤立性肿瘤小鼠模型的建立PMID:日期:2026-09-19This protocol outlines the detailed steps for generating a colorectal cancer liver metastasis (CRCLM) mouse model using three complementary approaches: i) portal venous seeding of CRCLM cells to simulate tumor cell dissemination through the portal circulation to the liver; ii) liver parenchymal implantation of CRCLM solid tumors to generate single, localized lesions derived from tumors generated via the portal venous seeding; and iii) intrahepatic parenchymal injection of CRCLM cells to produce isolated tumors directly within the liver tissue. The protocol emphasizes precise tissue handling and preservation, ensuring high tumor take rates while minimizing peritoneal disease, a common complication among CRCLM mouse models. These refined methods offer reliable and reproducible CRCLM models, providing a robust tool for studying tumor-host interactions and conducting preclinical evaluations of potential therapies.
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8. Retinal Inflammation in Diabetes.
8. 糖尿病中的视网膜炎症PMID:日期:2026-09-19Diabetic retinopathy is a potentially blinding complication of diabetes mellitus and the leading cause of irreversible vision loss in the working-age population. Diabetic retinopathy has historically been thought of as a microvascular complication of diabetes, but more recent research has shown that retinal neurons and glia are affected before clinically detectable vascular alterations. Although treatments have been developed to address the vascular lesions of diabetic retinopathy, there are currently no treatments for the early-onset neuro-glial perturbations. Increasing evidence supports inflammation as a critical factor in the development of neuro-glial dysfunction in the diabetic retina. Inflammatory processes are further activated in retinal neurons themselves in response to diabetes. The current review focuses on inflammatory molecular and physiological changes in the diabetic retina. The emerging evidence for a relationship between retinal neurons and glia and the inflammatory cascade is explored.
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9. IL-17 and IL-6 Trans-Signaling Coordinates Mesothelial Vascular Endothelial Growth Factor Production and Angiogenesis in the Peritoneum.
9. IL-17和IL-6反式信号传导协调腹膜间皮细胞血管内皮生长因子的产生和血管生成PMID:日期:2026-09-19Peritoneal angiogenesis is a key determinant of long-term peritoneal dialysis outcomes, yet the contribution of IL-17 remains unclear. This study examined the association between IL-17 and peritoneal vascularity in patients undergoing peritoneal dialysis and defined mechanisms linking IL-17 to vascular endothelial growth factor (VEGF) expression in human peritoneal mesothelial cells. Peritoneal biopsies showed sparse IL-17 expression, but IL-17 positivity correlated with increased IL-6 and VEGF expression and higher CD31 microvessel density, indicating a coordinated pro-angiogenic network. In vitro, IL-17 induced IL-6 mRNA and protein in human peritoneal mesothelial cells in a time- and dose-dependent manner but did not directly stimulate VEGF. However, combined IL-17 and soluble IL-6 receptor markedly increased VEGF mRNA, promoter activity, and protein secretion, consistent with IL-6 trans-signaling. Genetic or antibody-mediated inhibition of IL-6 abolished VEGF induction, confirming IL-6 dependency. Mechanistically, VEGF induction by IL-17 + soluble IL-6 receptor was mediated by STAT3 and was independent of SP4, despite IL-6-dependent SP4 up-regulation. Promoter analysis identified a VEGF region (-1290/-791) required for responsiveness, containing AP-1 and NF-κB binding sites. STAT3 acted upstream of AP-1 activation through induction of c-FOS, whereas NF-κB contributed directly to promoter activation and indirectly by enhancing IL-6 expression. These findings identify IL-17 as an indirect driver of peritoneal angiogenesis via IL-6 trans-signaling and coordinated STAT3, AP-1, and NF-κB activation.
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10. Proteasome Dysfunction in Basal Keratinocytes Drives Epidermal Disruption and Dermal Inflammation.
10. 基底角质形成细胞中的蛋白酶体功能障碍驱动表皮破坏和真皮炎症PMID:日期:2026-08-31Epidermal keratinocyte differentiation and cell death are tightly regulated to maintain skin homeostasis, and their disruption leads to severe skin disorders. Proteasome dysfunction has been implicated in proteasome-associated autoinflammatory syndromes, which are characterized by dermal inflammation, as well as in keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome caused by mutations in proteasome maturation protein. However, skin manifestations in proteasome-related disorders have been attributed to distinct cellular origins, rendering it unclear whether keratinocyte-intrinsic proteasome dysfunction is a common driver of both epidermal pathology and dermal inflammation. Here, it is demonstrated that keratinocyte-specific deletion of the standard proteasome subunit β5 results in neonatal lethality associated with complete loss of the epidermis. Inducible deletion of β5 in basal keratinocytes led to impaired epidermal differentiation, reduced proliferation, and apoptosis, accompanied by accumulation of ubiquitinated proteins without evidence of endoplasmic reticulum stress. Notably, proteasome dysfunction induced epidermal hyperplasia with spongiosis, followed by epidermolysis. Although this genetic alteration was restricted to keratinocytes, pronounced infiltration of neutrophils and macrophages was observed in the dermis, together with elevated expression of inflammatory mediators. These findings demonstrate that proteasome dysfunction in basal keratinocytes disrupts epidermal integrity and triggers secondary dermal inflammation, providing insight into the skin pathology associated with proteasome-related disorders.