American Journal of Pathology最新文献_第3页

This Month in AJP. 本月在AJP。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-09-09 DOI: 10.1016/j.ajpath.2025.09.001

引用次数: 0

Aldehyde Dehydrogenase 2 Deficiency Impairs Liver Progenitor Cell Proliferation in Alcohol-Fed Mice. 醛脱氢酶2缺乏损害酒精喂养小鼠肝祖细胞增殖。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-09-03 DOI: 10.1016/j.ajpath.2025.08.004

Peng Xiao, Siting Yang, Shenghua Bi, Yawen Hao, Feiyu Zhang, Lin Ru, Tao Liu, Shengying Qian, Qiuhong Zai, Ningning Ma, Junqi Niu, Yong He, Yanhang Gao

{"title":"Aldehyde Dehydrogenase 2 Deficiency Impairs Liver Progenitor Cell Proliferation in Alcohol-Fed Mice.","authors":"Peng Xiao, Siting Yang, Shenghua Bi, Yawen Hao, Feiyu Zhang, Lin Ru, Tao Liu, Shengying Qian, Qiuhong Zai, Ningning Ma, Junqi Niu, Yong He, Yanhang Gao","doi":"10.1016/j.ajpath.2025.08.004","DOIUrl":"10.1016/j.ajpath.2025.08.004","url":null,"abstract":"Aldehyde dehydrogenase 2 (ALDH2) is a critical enzyme involved in the detoxification of acetaldehyde. Although numerous studies have demonstrated the significance of ALDH2 in alcohol-associated liver disease, its role in alcohol-induced activation of liver progenitor cells (LPCs) has not been thoroughly investigated. Proteomic analysis of serum samples from patients with either normal ALDH2 genotype or ALDH2 mutation following alcohol consumption revealed that ALDH2 deficiency may suppress LPC proliferation. To test this hypothesis, Aldh2 knockout (Aldh2KO) mice were generated and fed a 3,5-diethoxycarbonyl1,4-dihydrocollidine-supplemented diet along with 10% ethanol in drinking water. A significant inhibition of LPC proliferation was observed in Aldh2KO mice after alcohol exposure, as indicated by reduced numbers of PanCK- and Ki-67-positive cells in the liver. Bulk RNA sequencing revealed that differentially expressed genes (DEGs) in 3,5-diethoxycarbonyl1,4-dihydrocollidine plus ethanol-fed Aldh2KO mice were enriched in pathways related to inflammation (up-regulated DEGs) and cell cycle suppression (down-regulated DEGs) based on Reactome pathway analysis compared with wild-type mice. Mechanistically, alcohol exposure in Aldh2KO mice led to reduced LPC proliferation, likely mediated by enhanced hepatic pyroptosis and inflammatory responses. In conclusion, these findings suggest that ALDH2 deficiency appears to impair LPC proliferation in alcohol-associated liver disease, highlighting the critical role of ALDH2 in liver regeneration following alcohol-induced injury.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel Perineural Pathways and the Dynamics of SIV-Infected Macrophage Trafficking Out of the Central Nervous System. 新的神经周围通路和猴免疫缺陷病毒感染的巨噬细胞运输出中枢神经系统的动力学。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-09-02 DOI: 10.1016/j.ajpath.2025.07.014

Zoey K Wallis, Yingshan Wei, Lily M Ceraso, Cecily C Midkiff, Addison Q Amadeck, Yiwei Wang, Andrew D Miller, Robert V Blair, Kenneth C Williams

{"title":"Novel Perineural Pathways and the Dynamics of SIV-Infected Macrophage Trafficking Out of the Central Nervous System.","authors":"Zoey K Wallis, Yingshan Wei, Lily M Ceraso, Cecily C Midkiff, Addison Q Amadeck, Yiwei Wang, Andrew D Miller, Robert V Blair, Kenneth C Williams","doi":"10.1016/j.ajpath.2025.07.014","DOIUrl":"10.1016/j.ajpath.2025.07.014","url":null,"abstract":"A challenge to eradicate HIV is the central nervous system (CNS) reservoir and unknown mechanisms-pathways by which infected macrophages can exit. We used intracisternal injection of superparamagnetic iron oxide nanoparticles (SPIONs), some of which had different internal immune fluorescence to define perineural pathways of SPION+ macrophage traffic in SIV-infected animals with AIDS, on antiretroviral therapy (ART) and with ART interruption. SPION+ macrophages are identified in central (spinal cord and cranial nerves) and peripheral (dorsal root ganglia) sites. In noninfected animals, SPION+ macrophages traffic out normally. With SIV infection, SPION+ macrophages accumulate in the CNS, and there are decreased numbers that traffic out. SIV- RNA and gp41 SPION+ macrophages are found in cranial nerves and dorsal root ganglion that are significantly reduced, but not eliminated, with ART. Using SPIONs with two different internal fluorescences, injected early and late after SIV infection, we find AIDS animals have greater numbers of early injected SPION+ macrophages within cranial nerves, consistent with reduced traffic late. With ART, there are greater numbers of late and dual (early and late) labeled SPION+ macrophages in the periphery, that return to levels found in AIDS animals following ART interruption. These findings reveal a novel pathway by which CNS macrophages can redistribute virus from the CNS to the periphery that persists despite ART.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Sugar-Coated Truth of Alcohol-Associated Liver Disease: Galectins as Multifaceted Regulators of Alcohol-Induced Liver Injury. 酒精相关肝病的糖衣真相：半乳糖凝集素作为酒精性肝损伤的多方面调节因子

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-08-26 DOI: 10.1016/j.ajpath.2025.07.013

Doug Terry, Brian S Robinson

引用次数: 0

The Role of Perivascular Adipose Tissue, White Adipose Tissue, and Brown Adipose Tissue in the Pathophysiological Effects of Ethanol. 血管周围脂肪组织、白色脂肪组织和棕色脂肪组织在乙醇病理生理效应中的作用。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-08-26 DOI: 10.1016/j.ajpath.2025.07.012

Thales M H Dourado, Carlos R Tirapelli

{"title":"The Role of Perivascular Adipose Tissue, White Adipose Tissue, and Brown Adipose Tissue in the Pathophysiological Effects of Ethanol.","authors":"Thales M H Dourado, Carlos R Tirapelli","doi":"10.1016/j.ajpath.2025.07.012","DOIUrl":"10.1016/j.ajpath.2025.07.012","url":null,"abstract":"Adipose tissue plays a crucial role in energy storage, but it also acts as an endocrine organ by secreting hormones and proinflammatory molecules. It regulates various processes, including adipogenesis, metabolism, and inflammation. White and brown adipose tissue (WAT and BAT) consists of white and brown adipocytes, respectively, which differ in cellular structure and function. Adipocytes also make up a significant part of perivascular adipose tissue (PVAT), which forms a sheath-like structure around blood vessels. Current research indicates that WAT, BAT, and PVAT are negatively affected by ethanol (ethyl alcohol). The changes induced by ethanol in the storage, metabolic, and secretory functions of PVAT and WAT are linked to vascular and hepatic dysfunction. In this context, while adipose tissue is a target of the harmful effects of ethanol, it also contributes to its pathophysiological consequences. Although the function of BAT is impacted by ethanol, BAT exhibits a protective role against ethanol-induced liver disease. This review highlights both past and recent efforts to identify the mechanisms through which ethanol consumption alters adipocyte function, with a focus on findings from studies that explain the detrimental effects of ethanol on WAT and BAT, and discusses the interplay between adipose tissue and the liver, particularly its implications for alcoholic liver disease. Additionally, new data that elucidate the mechanisms underlying ethanol-induced dysfunction in PVAT are summarized.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections. 蛋白质病变中的蛋白质抑制网络：机制和相互联系。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-08-26 DOI: 10.1016/j.ajpath.2025.07.011

Dariusz Pytel, Jody Fromm Longo

{"title":"The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.","authors":"Dariusz Pytel, Jody Fromm Longo","doi":"10.1016/j.ajpath.2025.07.011","DOIUrl":"10.1016/j.ajpath.2025.07.011","url":null,"abstract":"Proteinopathies are neurodegenerative disorders that are characterized by accumulation of misfolded toxic protein aggregates that lead to synaptic and neuronal dysfunction. Although genetically, clinically, and pathologically distinct, a common feature of these diseases is disruption of protein homeostasis (proteostasis), which causes accumulation of misfolded proteins. The machinery mediating proteostasis exquisitely balances and interlaces protein synthesis, protein folding and trafficking, and protein degradation processes within the proteostasis network to maintain homeostasis. The proteostasis network governs a functional and dynamic proteome by modulating the timing, location, and stoichiometry of protein expression, surveillance, and maintenance of protein folding and removal of misfolded or excess proteins. Although a functional proteome is essential for the health of all cell types, this is especially true for neurons, which are prone to enhanced cellular stress. Aging is the most important risk factor for proteostasis decline and the development of proteinopathies. However, germline and somatic mutations can also functionally impair components of the proteostasis network. Post-mitotic cells, particularly neurons, are rendered further susceptible to proteostasis dysfunction because of their extended lifespan. This review discusses the interconnections between the functional components mediating proteostasis in neuronal cells and how aberrations in proteostasis contribute to neuronal dysfunction and disease.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipid Droplet Dynamics in Alcoholic Steatohepatitis. 酒精性脂肪性肝炎的脂滴动力学。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-08-26 DOI: 10.1016/j.ajpath.2025.07.010

Delia Y Omar, Mathilda M Willoughby, Nourhan Mostafa, Kelly Otakhor, Saumya Bhatt, Mohammad A Abbas Zaidi, Micah B Schott

{"title":"Lipid Droplet Dynamics in Alcoholic Steatohepatitis.","authors":"Delia Y Omar, Mathilda M Willoughby, Nourhan Mostafa, Kelly Otakhor, Saumya Bhatt, Mohammad A Abbas Zaidi, Micah B Schott","doi":"10.1016/j.ajpath.2025.07.010","DOIUrl":"10.1016/j.ajpath.2025.07.010","url":null,"abstract":"Alcohol-associated liver disease poses a significant global health burden, with alcoholic steatohepatitis (ASH) representing a severe subtype driven by chronic alcohol consumption, hepatic inflammation, and limited treatment options. Central to ASH pathogenesis is the dysregulation of lipid droplet (LD) dynamics in hepatocytes. This review explores the critical role of LDs, focusing on alcohol-induced disruptions in LD biogenesis and catabolism. Chronic ethanol exposure enhances LD biogenesis from lipid import and de novo lipogenesis, while impairing LD catabolism by inhibiting lipolysis and lipophagy. Also, the review article examines alcohol's effect on remodeling the LD proteome and lipidome, including post-translational modifications. Additionally, LDs emerge as morphologic markers in hepatic stellate cells, where their loss drives fibrosis. Recent advances highlight potential therapeutic targets, such as restoring lipophagy or modulating LD biogenesis, offering hope for effective ASH treatments. This review underlines LDs as pivotal organelles in ASH progression and therapeutic innovation.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Navigating the Road to Progress in Neurodegeneration 指引神经退行性变的进展之路

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-08-22 DOI: 10.1016/j.ajpath.2025.02.010

Yomna Badawi , Christi L. Kolarcik

引用次数: 0

This Month in AJP 本月在AJP。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-08-08 DOI: 10.1016/j.ajpath.2025.08.001

引用次数: 0

Exploring Vascular Contributions to Cognitive Impairment: Small-Vessel Disease of White Matter and Microplastics/Nanoplastics. 探索血管对认知障碍的贡献：白质和微/纳米塑料的小血管疾病。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-08-08 DOI: 10.1016/j.ajpath.2025.07.007

Elaine L Bearer

{"title":"Exploring Vascular Contributions to Cognitive Impairment: Small-Vessel Disease of White Matter and Microplastics/Nanoplastics.","authors":"Elaine L Bearer","doi":"10.1016/j.ajpath.2025.07.007","DOIUrl":"10.1016/j.ajpath.2025.07.007","url":null,"abstract":"Cognitive impairment due to vascular pathology was recognized by Otto Binswanger in 1894, before Alois Alzheimer presented his findings in 1907. Vascular causes of cognitive impairment are likely due to a range of pathologies that are still, a hundred years later, unknown. Recent epidemiologic evidence from post-mortem human brains reports cases may be afflicted by Alzheimer disease, vascular disease, or both. Although it is well known that hypertension and diabetes affect vasculature throughout the body as well as brain, other types of underlying causes that primarily affect cerebral vessels are understudied. Consensus guidelines exist for histopathologic diagnosis of Alzheimer disease, but are limited for cerebrovascular diseases. Here, first, the anatomy of brain vasculature is reviewed. Next, a schema for categorization of vascular pathologies is proposed, followed by examples that illustrate these pathologies together with stains useful for their detection. Scoring pathologies across many cases according to this schema will subdivide vascular dementias into their underlying, potentially treatable, categories. The recent discovery of microplastics/nanoplastics in the brain and their association with vasculature will have a profound influence on how vascular-pathology-associated cognitive impairment is understood and diagnosed. Going forward, anatomic pathologists will need to apply this categorization to triage types of cerebrovascular pathology and begin to dissect its underlying causes, consequences, and potential treatments.","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0