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  1. Article ; Online: Sinusoidal endotheliopathy in nonalcoholic steatohepatitis: therapeutic implications.

    Ibrahim, Samar H

    American journal of physiology. Gastrointestinal and liver physiology

    2021  Volume 321, Issue 1, Page(s) G67–G74

    Abstract: Liver sinusoidal endothelial cells (LSECs) are distinct subtypes of endothelial cells lining a low flow vascular bed at the interface of the liver parenchyma and the circulating immune cells and soluble factors. Emerging literature implicates LSEC in the ...

    Abstract Liver sinusoidal endothelial cells (LSECs) are distinct subtypes of endothelial cells lining a low flow vascular bed at the interface of the liver parenchyma and the circulating immune cells and soluble factors. Emerging literature implicates LSEC in the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD). During the evolution of NAFLD, LSEC dysfunction ensues. LSECs undergo morphological and functional transformation known as "capillarization," as well as a pathogenic increase in surface adhesion molecules expression, referred to in this review as "endotheliopathy." LSECs govern the composition of hepatic immune cell populations in nonalcoholic steatohepatis (NASH) by mediating leukocyte subset adhesion through specific combinations of activated adhesion molecules and secreted chemokines. Moreover, extracellular vesicles released by hepatocyte under lipotoxic stress in NASH act as a catalyst for the inflammatory response and promote immune cell chemotaxis and adhesion. In the current review, we highlight leukocyte adhesion to LSEC as an initiating event in the sterile inflammatory response in NASH. We discuss preclinical studies targeting immune cells adhesion in NASH mouse models and potential therapeutic anti-inflammatory strategies for human NASH.
    MeSH term(s) Animals ; Cell Adhesion/physiology ; Endothelial Cells/metabolism ; Hepatocytes/metabolism ; Humans ; Inflammation/therapy ; Liver/metabolism ; Liver/physiopathology ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/metabolism ; Non-alcoholic Fatty Liver Disease/therapy
    Language English
    Publishing date 2021-05-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00009.2021
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  2. Article ; Online: Severe Acute Hepatitis of Unknown Etiology in Children: New Virus or Immune Dysregulation.

    Gutierrez Sanchez, Luz Helena / Ibrahim, Samar H

    Gastroenterology

    2024  

    Language English
    Publishing date 2024-04-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2024.04.016
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  3. Article ; Online: The Global Alagille Alliance study: Redefining the natural history of Alagille syndrome.

    Habash, Nawras / Ibrahim, Samar H

    Hepatology (Baltimore, Md.)

    2022  Volume 77, Issue 2, Page(s) 347–349

    MeSH term(s) Humans ; Alagille Syndrome
    Language English
    Publishing date 2022-09-17
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.32760
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  4. Article ; Online: Utilization and perspectives of weight loss medications in pediatric metabolic dysfunction-associated steatotic liver disease.

    Kehar, Mohit / Ibrahim, Samar H / Ramirez, Charina M / Amin, Saista Asif / Diamond, Tamir / Mohammad, Saeed

    Journal of pediatric gastroenterology and nutrition

    2024  

    Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing globally in pediatric populations. Currently, MASLD management primarily relies on lifestyle interventions, which pose challenges in sustaining long-term weight loss. This ... ...

    Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing globally in pediatric populations. Currently, MASLD management primarily relies on lifestyle interventions, which pose challenges in sustaining long-term weight loss. This study investigated the use of weight loss medications in MASLD care through an international survey of 166 pediatric gastroenterologists and hepatologists. The results indicated a notable interest in weight loss medications, with 38% of practitioners considering or using them, particularly glucagon-like peptide-1 receptor agonists. However, the survey also revealed a tendency among clinicians to refer patients to specialists, emphasizing the potential gap between acknowledgment and prescription practices. Challenges include the lack of guidelines and uncertainty regarding side effects. The study highlights a pressing need for education, with over 90% of the respondents expressing an interest. Our study highlights the current management of MASLD, the potential role of pharmacotherapy, and highlights avenues for improved care and education in this dynamic field.
    Language English
    Publishing date 2024-05-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603201-1
    ISSN 1536-4801 ; 0277-2116
    ISSN (online) 1536-4801
    ISSN 0277-2116
    DOI 10.1002/jpn3.12236
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  5. Article ; Online: Digital pathology and spatial omics in steatohepatitis: Clinical applications and discovery potentials.

    Meroueh, Chady / Warasnhe, Khaled / Tizhoosh, Hamid R / Shah, Vijay H / Ibrahim, Samar H

    Hepatology (Baltimore, Md.)

    2024  

    Abstract: Steatohepatitis with diverse etiologies is the most common histological manifestation in patients with liver disease. However, there are currently no specific histopathological features pathognomonic for metabolic dysfunction-associated steatotic liver ... ...

    Abstract Steatohepatitis with diverse etiologies is the most common histological manifestation in patients with liver disease. However, there are currently no specific histopathological features pathognomonic for metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, or metabolic dysfunction-associated steatotic liver disease with increased alcohol intake. Digitizing traditional pathology slides has created an emerging field of digital pathology, allowing for easier access, storage, sharing, and analysis of whole-slide images. Artificial intelligence (AI) algorithms have been developed for whole-slide images to enhance the accuracy and speed of the histological interpretation of steatohepatitis and are currently employed in biomarker development. Spatial biology is a novel field that enables investigators to map gene and protein expression within a specific region of interest on liver histological sections, examine disease heterogeneity within tissues, and understand the relationship between molecular changes and distinct tissue morphology. Here, we review the utility of digital pathology (using linear and nonlinear microscopy) augmented with AI analysis to improve the accuracy of histological interpretation. We will also discuss the spatial omics landscape with special emphasis on the strengths and limitations of established spatial transcriptomics and proteomics technologies and their application in steatohepatitis. We then highlight the power of multimodal integration of digital pathology augmented by machine learning (ML)algorithms with spatial biology. The review concludes with a discussion of the current gaps in knowledge, the limitations and premises of these tools and technologies, and the areas of future research.
    Language English
    Publishing date 2024-03-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1097/HEP.0000000000000866
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  6. Article ; Online: The evolving role of liver sinusoidal endothelial cells in liver health and disease.

    McConnell, Matthew J / Kostallari, Enis / Ibrahim, Samar H / Iwakiri, Yasuko

    Hepatology (Baltimore, Md.)

    2023  Volume 78, Issue 2, Page(s) 649–669

    Abstract: LSECs are a unique population of endothelial cells within the liver and are recognized as key regulators of liver homeostasis. LSECs also play a key role in liver disease, as dysregulation of their quiescent phenotype promotes pathological processes ... ...

    Abstract LSECs are a unique population of endothelial cells within the liver and are recognized as key regulators of liver homeostasis. LSECs also play a key role in liver disease, as dysregulation of their quiescent phenotype promotes pathological processes within the liver including inflammation, microvascular thrombosis, fibrosis, and portal hypertension. Recent technical advances in single-cell analysis have characterized distinct subpopulations of the LSECs themselves with a high resolution and defined their gene expression profile and phenotype, broadening our understanding of their mechanistic role in liver biology. This article will review 4 broad advances in our understanding of LSEC biology in general: (1) LSEC heterogeneity, (2) LSEC aging and senescence, (3) LSEC role in liver regeneration, and (4) LSEC role in liver inflammation and will then review the role of LSECs in various liver pathologies including fibrosis, DILI, alcohol-associated liver disease, NASH, viral hepatitis, liver transplant rejection, and ischemia reperfusion injury. The review will conclude with a discussion of gaps in knowledge and areas for future research.
    MeSH term(s) Humans ; Endothelial Cells/metabolism ; Liver/pathology ; Liver Diseases/pathology ; Fibrosis ; Inflammation/metabolism
    Language English
    Publishing date 2023-01-03
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1097/HEP.0000000000000207
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  7. Article ; Online: Omega-3 Fatty Acid-rich Parenteral Nutrition: Is It a Double-edged Sword?

    Ibrahim, Samar H

    Journal of pediatric gastroenterology and nutrition

    2016  Volume 62, Issue 5, Page(s) e46–7

    Language English
    Publishing date 2016-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603201-1
    ISSN 1536-4801 ; 0277-2116
    ISSN (online) 1536-4801
    ISSN 0277-2116
    DOI 10.1097/MPG.0000000000001091
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  8. Article ; Online: Extracellular Vesicles in Hepatobiliary Health and Disease.

    Parthasarathy, Gopanandan / Hirsova, Petra / Kostallari, Enis / Sidhu, Guneet S / Ibrahim, Samar H / Malhi, Harmeet

    Comprehensive Physiology

    2023  Volume 13, Issue 3, Page(s) 4631–4658

    Abstract: Extracellular vesicles (EVs) are membrane-bound nanoparticles released by cells and are an important means of intercellular communication in physiological and pathological states. We provide an overview of recent advances in the understanding of EV ... ...

    Abstract Extracellular vesicles (EVs) are membrane-bound nanoparticles released by cells and are an important means of intercellular communication in physiological and pathological states. We provide an overview of recent advances in the understanding of EV biogenesis, cargo selection, recipient cell effects, and key considerations in isolation and characterization techniques. Studies on the physiological role of EVs have relied on cell-based model systems due to technical limitations of studying endogenous nanoparticles in vivo . Several recent studies have elucidated the mechanistic role of EVs in liver diseases, including nonalcoholic fatty liver disease, viral hepatitis, cholestatic liver disease, alcohol-associated liver disease, acute liver injury, and liver cancers. Employing disease models and human samples, the biogenesis of lipotoxic EVs downstream of endoplasmic reticulum stress and microvesicles via intracellular activation stress signaling are discussed in detail. The diverse cargoes of EVs including proteins, lipids, and nucleic acids can be enriched in a disease-specific manner. By carrying diverse cargo, EVs can directly confer pathogenic potential, for example, recruitment and activation of monocyte-derived macrophages in NASH and tumorigenicity and chemoresistance in hepatocellular carcinoma. We discuss the pathogenic role of EVs cargoes and the signaling pathways activated by EVs in recipient cells. We review the literature that EVs can serve as biomarkers in hepatobiliary diseases. Further, we describe novel approaches to engineer EVs to deliver regulatory signals to specific cell types, and thus use them as therapeutic shuttles in liver diseases. Lastly, we identify key lacunae and future directions in this promising field of discovery and development. © 2023 American Physiological Society. Compr Physiol 13:4631-4658, 2023.
    MeSH term(s) Humans ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/pathology ; Non-alcoholic Fatty Liver Disease/metabolism ; Models, Biological ; Biological Transport
    Language English
    Publishing date 2023-06-26
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2040-4603
    ISSN (online) 2040-4603
    DOI 10.1002/cphy.c210046
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  9. Article ; Online: Endotheliopathy in the metabolic syndrome: Mechanisms and clinical implications.

    Furuta, Kunimaro / Tang, Xiaofang / Islam, Shahidul / Tapia, Alonso / Chen, Zhen Bouman / Ibrahim, Samar H

    Pharmacology & therapeutics

    2023  Volume 244, Page(s) 108372

    Abstract: The increasing prevalence of the metabolic syndrome (MetS) is a threat to global public health due to its lethal complications. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the MetS characterized by hepatic steatosis, which is ...

    Abstract The increasing prevalence of the metabolic syndrome (MetS) is a threat to global public health due to its lethal complications. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the MetS characterized by hepatic steatosis, which is potentially progressive to the inflammatory and fibrotic nonalcoholic steatohepatitis (NASH). The adipose tissue (AT) is also a major metabolic organ responsible for the regulation of whole-body energy homeostasis, and thereby highly involved in the pathogenesis of the MetS. Recent studies suggest that endothelial cells (ECs) in the liver and AT are not just inert conduits but also crucial mediators in various biological processes via the interaction with other cell types in the microenvironment both under physiological and pathological conditions. Herein, we highlight the current knowledge of the role of the specialized liver sinusoidal endothelial cells (LSECs) in NAFLD pathophysiology. Next, we discuss the processes through which AT EC dysfunction leads to MetS progression, with a focus on inflammation and angiogenesis in the AT as well as on endothelial-to-mesenchymal transition of AT-ECs. In addition, we touch upon the function of ECs residing in other metabolic organs including the pancreatic islet and the gut, the dysregulation of which may also contribute to the MetS. Finally, we highlight potential EC-based therapeutic targets for human MetS, and NASH based on recent achievements in basic and clinical research and discuss how to approach unsolved problems in the field.
    MeSH term(s) Humans ; Non-alcoholic Fatty Liver Disease/metabolism ; Metabolic Syndrome/metabolism ; Endothelial Cells/metabolism ; Liver/metabolism ; Liver Cirrhosis/complications
    Language English
    Publishing date 2023-03-07
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 194735-7
    ISSN 1879-016X ; 0163-7258
    ISSN (online) 1879-016X
    ISSN 0163-7258
    DOI 10.1016/j.pharmthera.2023.108372
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    Zs.A 1183: Show issues Location:
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  10. Article ; Online: Reply.

    Ibrahim, Samar H / Kamath, Binita M / Loomes, Kathleen M / Karpen, Saul J

    Hepatology (Baltimore, Md.)

    2022  Volume 76, Issue 2, Page(s) E47

    Language English
    Publishing date 2022-04-07
    Publishing country United States
    Document type Letter
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.32493
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