American Journal of Pathology最新文献_第8页

From Theory to Practice 从理论到实践：腹膜假性黏液瘤研究综述及其对未来治疗的意义。

IF 3.6 2区医学 Q1 PATHOLOGY

American Journal of Pathology

Pub Date : 2025-09-11 DOI: 10.1016/j.ajpath.2025.08.005

Han Gao , Hongli Wang , Xiufeng Li , Fulei Zhang , Yiru Ba , Jiatong Zhao , Chengwei He , Shuzi Xin , Xiaohui Liu , Guowei Liang

Pseudomyxoma peritonei (PMP) is a rare disease characterized by symptoms such as mucinous ascites and omental cake, typically arising from a perforated epithelial tumor of the appendix. Because of its rarity, non-specific histologic characteristics, and slow progression, its pathogenesis and optimal treatment remain subjects of debate. PMP is still a challenging and enigmatic condition. Increasing global attention is being directed toward understanding its pathogenesis and establishing standard treatment approaches. PMP and mucin are inextricably linked. This article highlighted the important role of mucin in the disease's pathogenesis. It also discussed several potential therapeutic strategies for eliminating mucin in PMP. Tumor development and metastasis involve a series of steps that include the interaction between the tumor and the host-derived stromal environment, which promotes angiogenesis and activation of inflammatory cells. Inflammatory cytokines and chemokines play a crucial role in the progression and development of PMP. The microbiome and specific microorganisms may directly influence tumor development, progression, and responses to certain therapies in PMP. Thus, the article summarized the interactions among bacteria, the immune system, and mucin in PMP, focusing on the mechanisms that related to abnormal mucin and tumor growth. This review critically examined the existing literature on the clinical features, pathologic processes, and treatment options in PMP, aiming to guide future research toward identifying novel therapeutic targets and gut-related disease biomarkers.

腹膜假性粘液瘤（PMP）是一种罕见的疾病，其症状为粘液性腹水和大网膜饼，通常由阑尾穿孔的上皮肿瘤引起。由于其罕见性、非特异性的组织学特征和缓慢的进展，其发病机制和最佳治疗仍然是争论的主题。PMP仍然是一个具有挑战性和神秘的条件。越来越多的全球关注的方向是了解其发病机制和建立标准的治疗方法。PMP和粘蛋白有着千丝万缕的联系。本文强调粘蛋白在本病发病机制中的重要作用。本文还讨论了几种消除PMP中粘蛋白的潜在治疗策略。肿瘤的发展和转移涉及一系列步骤，包括肿瘤与宿主源性基质环境的相互作用，促进血管生成和炎症细胞的激活。炎症因子和趋化因子在PMP的进展和发展中起着至关重要的作用。微生物组和特定微生物可能直接影响PMP的肿瘤发生、进展和对某些治疗的反应。因此，本文综述了PMP中细菌、免疫系统和粘蛋白的相互作用，重点探讨了粘蛋白异常与肿瘤生长的相关机制。本文对PMP的临床特征、病理过程和治疗方案进行了综述，旨在指导未来的研究，以确定新的治疗靶点和肠道相关疾病的生物标志物。

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引用次数: 0

Laminin Receptors in Peripheral Tissues 外周组织层粘连蛋白受体——敲除小鼠分析揭示的功能。

IF 3.6 2区医学 Q1 PATHOLOGY

American Journal of Pathology

Pub Date : 2025-09-11 DOI: 10.1016/j.ajpath.2025.08.007

Wanling Xuan , Yao Yao

Laminin, by interacting with its receptors (mainly integrins and dystroglycan), exerts a variety of important functions in multiple organs. Loss-of-function studies have described the essential roles of laminin receptors in both physiological and pathologic conditions. This review summarizes the pathology and loss-of-function phenotypes of laminin receptors, including integrin-α3, integrin-α6, integrin-α7, integrin-β1, integrin-β4, and dystroglycan, focusing on the skin, kidney, skeletal muscle, peripheral nervous system, mammary gland, lung, and heart. To explore the functional redundancy/compensation among different laminin receptors, the phenotypes of compound knockout mice are compared with that of single mutants. Next, key signaling pathways downstream of each laminin receptor are summarized and compared. In addition, key questions in the field and future directions are also discussed. The aim of this review was to provide a synthetic review on loss-of-function studies of laminin receptors and foster the formation and testing of new hypotheses in the field.

层粘连蛋白通过与其受体（主要是整合素和糖酐）相互作用，在多个器官中发挥多种重要功能。功能丧失研究已经证明了层粘连蛋白受体在生理和病理条件下的重要作用。本文综述了层粘连蛋白受体的病理和功能丧失表型，包括整合素-α3、-α6、-α7、-β1、-β4和糖酐异常，重点介绍了皮肤、肾脏、骨骼肌、周围神经系统、乳腺、肺和心脏。为了探索不同层粘连蛋白受体之间的功能冗余/补偿，我们将复合敲除小鼠的表型与单突变小鼠的表型进行了比较。接下来，总结和比较各层粘连蛋白受体下游的关键信号通路。此外，还对该领域的关键问题和未来发展方向进行了讨论。本文旨在对层粘连蛋白受体功能丧失的研究进行综述，并促进该领域新假设的形成和检验。

引用次数: 0

The Role of Extracellular Vesicle–Derived miRNA in the Atherosclerotic Burden 细胞外囊泡来源的miRNA在动脉粥样硬化负担中的作用。

IF 3.6 2区医学 Q1 PATHOLOGY

American Journal of Pathology

Pub Date : 2025-09-11 DOI: 10.1016/j.ajpath.2025.08.006

Alessandra S. Rizzuto , Isabella Fichtner , Stefano Carugo , Annalisa Radeghieri , Chiara Macchi , Massimiliano Ruscica

In the context of atheroma-related sequelae, the role of extracellular vesicles (EVs) continues to spike interest. Their ability to traffic molecular cargo between cells highlights their role in intercellular communication, and consequently their involvement in mediating molecular events at the basis of physiological and pathologic processes. EVs encapsulate miRNAs within their lumen, shielding them from circulating ribonucleases, which would otherwise catalyze their degradation. However, there is an ongoing debate regarding the implication of miRNA contained within EVs in modulating biological activities on a molecular level. Therefore, the aim of the present review is to discuss the role of EV-derived miRNA, focusing on their implication in molecular mechanisms underlying atheroma formation. EVs of endothelial origin can regulate monocyte activation by transferring miR-10a that targets components of the inflammatory pathway. Tail vein administration of EVs derived from endothelial cells enriched in miR-34c-5p markedly reduces atherosclerosis progression. In patients with stable coronary artery disease, elevated levels of miR-126 and miR-199a in circulating EVs are significantly associated with a reduced incidence of major adverse cardiovascular event rate. These nanoparticles, released by all cells into most biological fluids, hold promise as a liquid biopsy tool as their circulating patterns and cargo can reflect the onset and severity of cardiovascular diseases.

在动脉粥样硬化相关后遗症的背景下，细胞外囊泡（EVs）的作用继续引起人们的兴趣。它们在细胞间运输分子货物的能力突出了它们在细胞间通讯中的作用，因此它们在生理和病理过程的基础上参与介导分子事件。电动汽车将mirna封装在其腔内，保护它们不受循环核糖核酸酶的影响，否则核糖核酸酶会催化它们的降解。然而，关于ev中含有的microRNA （miR）在分子水平上调节生物活性的意义，一直存在争议。因此，本综述的目的是讨论ev衍生的miR的作用，重点讨论它们在动脉粥样硬化形成的分子机制中的意义。内皮来源的EVs可以通过传递靶向炎症通路成分的miR-10a来调节单核细胞活化。尾静脉给药来源于富集miR-34c-5p的内皮细胞的ev可显著降低动脉粥样硬化的进展。在稳定性冠状动脉疾病患者中，循环ev中miR-126和miR-199a水平升高与主要不良心血管事件发生率降低显著相关。这些由所有细胞释放到大多数生物液体中的纳米颗粒有望作为液体活检工具，因为它们的循环模式和货物可以反映心血管疾病的发病和严重程度。

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引用次数: 0

This Month in AJP 本月在AJP。

IF 3.6 2区医学 Q1 PATHOLOGY

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 Q1 PATHOLOGY

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

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 pan-cytokeratin (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.

醛脱氢酶2 （ALDH2）是参与乙醛解毒的关键酶。尽管大量研究已经证明ALDH2在酒精相关性肝病（ALD）中的重要意义，但其在酒精诱导的肝祖细胞（LPCs）活化中的作用尚未得到充分研究。对ALDH2基因型正常或ALDH2基因型突变患者的血清样本进行蛋白质组学分析显示，ALDH2缺乏可能抑制LPC增殖。为了验证这一假设，我们培育了Aldh2敲除（Aldh2KO）小鼠，并给它们喂食添加了3,5-二氧羰基1,4-二氢碰撞碱（DDC）的饮食，同时在饮用水中添加10%的乙醇。酒精暴露后，Aldh2KO小鼠的LPC增殖明显受到抑制，肝脏中panck和ki67阳性细胞数量减少。大量RNA测序（RNA-seq）显示，与野生型（WT）小鼠相比，基于Reactome通路分析，DDC加乙醇喂养的Aldh2KO小鼠中差异表达基因（DEGs）在炎症（DEGs上调）和细胞周期抑制（DEGs下调）相关通路中富集。在机制上，酒精暴露在Aldh2KO小鼠中导致LPC增殖减少，可能是由肝焦亡和炎症反应增强介导的。总之，这些发现表明，ALDH2缺乏似乎会损害ALD中LPC的增殖，突出了ALDH2在酒精诱导损伤后肝脏再生中的关键作用。

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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 Q1 PATHOLOGY

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

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 SIV-glycoprotein 41 (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.

根除艾滋病毒的一个挑战是中枢神经系统的储存库和未知的机制-被感染的巨噬细胞可以退出的途径。我们采用腹腔注射超顺磁性氧化铁纳米颗粒（SPION），其中一些具有不同的内部免疫荧光，以确定SIV感染的艾滋病动物、抗逆转录病毒治疗和抗逆转录病毒治疗中断时SPION+巨噬细胞运输的神经周围通路。SPION+巨噬细胞见于中枢（脊髓和脑神经）和外周（背根神经节）部位。在未感染动物中，SPION+巨噬细胞正常输出。SIV感染时，SPION+巨噬细胞在中枢神经系统内积聚，流出的数量减少。在脑神经和DRG中发现SIV- RNA和gp41 SPION+巨噬细胞，ART显著减少，但未消除。通过在SIV感染早期和晚期注射两种不同内部荧光的SPION，我们发现艾滋病动物早期在脑神经内注射的SPION+巨噬细胞数量更多，与后期交通量减少一致。在抗逆转录病毒治疗中，外周有更多的晚期和双（早期和晚期）标记SPION+巨噬细胞，它们在抗逆转录病毒治疗中断后恢复到艾滋病动物的水平。这些发现揭示了一种新的途径，通过这种途径，中枢神经系统巨噬细胞可以将病毒从中枢神经系统重新分配到外周，尽管抗逆转录病毒疗法仍然存在。

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引用次数: 0

The Sugar-Coated Truth of Alcohol-Associated Liver Disease 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 Q1 PATHOLOGY

American Journal of Pathology

Pub Date : 2025-08-26 DOI: 10.1016/j.ajpath.2025.07.013

Doug Terry, Brian S. Robinson

Alcohol-associated diver disease is a major driver of end-stage liver diseases globally. Alcohol functions as a hepatotoxin by overwhelming cell stress response pathways and deregulating hepatocellular protein, amino acid, and lipid metabolism. In addition, alcohol alters innate and adaptive inflammatory immune responses and acts on extrahepatic organs to flood the liver with pro-inflammatory stimuli. Here we examine how galectins, a class of highly conserved carbohydrate-binding proteins, regulate liver homeostasis and pathology. Next, we define how galectins affect key pathways that drive alcohol-induced liver disease, including hepatocyte cell biology (eg, altered lipid metabolism, endoplasmic reticulum and lysosomal stress, mitochondrial dysfunction), innate and immune response, intestinal dysfunction, and liver fibrosis. We then document the roles of galectins in the setting of alcohol-associated liver disease. Finally, we discuss galectins as theragnostic markers and therapeutic targets for alcohol-associated liver disease and address key open questions in the field.

酒精相关性肝病是全球终末期肝病的主要驱动因素。酒精作为一种肝毒素，通过压倒细胞应激反应途径和解除肝细胞蛋白质、氨基酸和脂质代谢的调节而发挥作用。此外，酒精改变先天和适应性炎症免疫反应，并作用于肝外器官，使肝脏充满促炎刺激。在这里，我们研究了凝集素，一类高度保守的碳水化合物结合蛋白，如何调节肝脏稳态和病理。接下来，我们定义了半乳糖凝集素如何影响驱动酒精诱导的肝脏疾病的关键途径，包括肝细胞细胞生物学（例如，脂质代谢改变、内质网和溶酶体应激、线粒体功能障碍）、先天和免疫反应、肠道功能障碍和肝纤维化。然后我们继续记录凝集素在酒精相关肝脏疾病中的作用。最后，我们讨论了凝集素作为酒精相关肝病的诊断标志物和治疗靶点，并解决了该领域的关键开放性问题。

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 Q1 PATHOLOGY

American Journal of Pathology

Pub Date : 2025-08-26 DOI: 10.1016/j.ajpath.2025.07.012

Thales M.H. Dourado , Carlos R. Tirapelli

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.

脂肪组织在能量储存中起着至关重要的作用，但它也作为内分泌器官分泌激素和促炎分子。它调节各种过程，包括脂肪生成、代谢和炎症。白色脂肪组织（WAT）和棕色脂肪组织（BAT）分别由白色脂肪细胞和棕色脂肪细胞组成，它们的细胞结构和功能不同。脂肪细胞也是血管周围脂肪组织（PVAT）的重要组成部分，PVAT在血管周围形成鞘状结构。目前的研究表明，WAT、BAT和PVAT受到乙醇（乙醇）的负面影响。乙醇引起的PVAT和WAT的储存、代谢和分泌功能的变化与血管和肝脏功能障碍有关。在这种情况下，虽然脂肪组织是乙醇有害影响的目标，但它也有助于其病理生理后果。虽然BAT的功能受到乙醇的影响，但它对乙醇诱导的肝脏疾病具有保护作用。这篇综述强调了过去和最近的努力，以确定通过乙醇消耗改变脂肪细胞功能的机制。我们将重点关注解释乙醇对WAT和BAT有害影响的研究结果，并讨论脂肪组织与肝脏之间的相互作用，特别是其对酒精性肝病（ALD）的影响。此外，我们总结了阐明乙醇诱导PVAT功能障碍机制的新数据。

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引用次数: 0

The Proteostasis Network in Proteinopathies 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 Q1 PATHOLOGY

American Journal of Pathology

Pub Date : 2025-08-26 DOI: 10.1016/j.ajpath.2025.07.011

Dariusz Pytel, Jody Fromm Longo

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.

蛋白质病是神经退行性疾病，其特征是错误折叠的有毒蛋白质聚集体的积累，导致突触和神经元功能障碍。尽管这些疾病在遗传、临床和病理上是不同的，但它们的一个共同特征是蛋白质稳态（proteostasis）被破坏，导致错误折叠蛋白质的积累。调节蛋白质平衡的机制巧妙地平衡和交错蛋白质合成，蛋白质折叠和运输，以及蛋白质降解过程在蛋白质平衡网络中维持稳态。蛋白质静止网络通过调节蛋白质表达的时间、位置和化学计量，监视和维持蛋白质折叠以及去除错误折叠或过量蛋白质来控制功能和动态蛋白质组。尽管功能性蛋白质组对所有细胞类型的健康都是必不可少的，但对于容易受到细胞压力增强的神经元来说尤其如此。衰老是蛋白质抑制能力下降和蛋白质病变发生的最重要的危险因素。然而，种系和体细胞突变也可以在功能上损害蛋白质静止网络的组成部分。有丝分裂后的细胞，特别是神经元，由于它们的寿命延长，更容易受到蛋白质平衡功能障碍的影响。本文就神经元细胞中介导蛋白质平衡的功能成分之间的相互联系以及蛋白质平衡异常如何导致神经元功能障碍和疾病进行了综述。

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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 Q1 PATHOLOGY

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

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.

酒精相关肝脏疾病（ALD）是全球重大的健康负担，酒精性脂肪性肝炎（ASH）是一种由慢性酒精摄入、肝脏炎症和有限治疗方案驱动的严重亚型。ASH发病机制的核心是肝细胞脂滴（LD）动力学失调。这篇综述探讨了LD的关键作用，重点是酒精诱导的LD生物发生和分解代谢的破坏。慢性乙醇暴露增强了脂质输入和新生脂肪生成（DNL）的LD生物发生，同时通过抑制脂肪分解和脂肪吞噬来损害LD分解代谢。此外，该综述研究了酒精对LD蛋白质组和脂质组重塑的影响，包括翻译后修饰。此外，ld作为肝星状细胞的形态学标记出现，它们的丢失导致肝纤维化。最近的进展突出了潜在的治疗靶点，如恢复脂肪吞噬或调节LD生物发生，为有效治疗ASH提供了希望。这篇综述强调ld是ASH进展和治疗创新的关键细胞器。

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引用次数: 0