tbuckley/cabot-search huggingface dataset:
Bright Light Therapy for Nonseasonal Depressive Disorders
Authors: Artur Menegaz de Almeida, Francisco Cezar Aquino de Moraes, Maria Eduarda Cavalcanti Souza, Jorge Henrique Cavalcanti Orestes Cardoso, Fernanda Tamashiro, Celso Miranda, Lilianne Fernandes, Michele Kreuz, Francinny Alves Kelly
Journal: JAMA Psychiatry (2024)

Importance Seasonal humor disorders are prone to have a link with daylight exposure. However, the effect of external light on nonseasonal disorders remains unclear. Evidence is lacking for the validity of bright light therapy (BLT) as an adjunctive treatment for these patients. Objective To assess BLT effectiveness as an adjunctive treatment for nonseasonal depressive disorders. Data Sources In March 2024, a comprehensive search was performed of publications in the MEDLINE, Embase, and Cochrane databases for randomized clinical trials (RCTs) evaluating BLT effects in patients with nonseasonal depression. Study Selection RCTs published since 2000 were eligible. Comparisons between BLT and dim red light or antidepressant monotherapy alone were considered for inclusion. Data Extraction and Synthesis Using the systematic review approach on RCTs published from January 1, 2000, through March 25, 2024, differences between patients treated with and without BLT were estimated using the Mantel-Haenszel method; heterogeneity was assessed using I 2 statistics. Main Outcomes and Measures Remission of symptoms, response to treatment rates, and depression scales were assessed. Results In this systematic review and meta-analysis of 11 unique trials with data from 858 patients (649 female [75.6%]), statistically significant better remission and response rates were found in the BLT group (remission: 40.7% vs 23.5%; odds ratio [OR], 2.42; 95% CI, 1.50-3.91; P &amp;amp;lt;.001; I 2 = 21%; response: 60.4% vs 38.6%; OR, 2.34; 95% CI, 1.46-3.75; P &amp;amp;lt;.001; I 2 = 41%). With BLT, subgroup analysis based on follow-up times also showed better remission (&amp;amp;lt;4 weeks: 27.4% vs 9.2%; OR, 3.59; 95% CI, 1.45-8.88; P = .005; I 2 = 0% and &amp;amp;gt;4 weeks: 46.6% vs 29.1%; OR, 2.18; 95% CI, 1.19-4.00; P = .01; I 2 = 47%) and response (&amp;amp;lt;4 weeks: 55.6% vs 27.4%; OR, 3.65; 95% CI, 1.81-7.33; P &amp;amp;lt;.001; I 2 = 35% and &amp;amp;gt;4 weeks: 63.0% vs 44.9%; OR, 1.79; 95% CI, 1.01-3.17; P = .04; I 2 = 32%) rates. Conclusions and Relevance Results of this systematic review and meta-analysis reveal that BLT was an effective adjunctive treatment for nonseasonal depressive disorders. Additionally, results suggest that BLT may improve the response time to the initial treatment.
Comprehensive Proteomic Profiling of Human Myocardium Reveals Signaling Pathways Dysregulated in Hypertrophic Cardiomyopathy
Authors: Heidi S Lumish, Mark V Sherrid, Paul M L Janssen, Giovanni Ferrari, Kohei Hasegawa, Estibaliz Castillero, Elizabeth Adlestein, Daniel G Swistel, Veli K Topkara, Mathew S Maurer, Muredach P Reilly, Yuichi J Shimada
Journal: Journal of the American College of Cardiology (2024)
Prevalence and Impact of Recurrent Rejection on Pediatric Heart Transplant Recipients
Authors: Shahnawaz Amdani, James K Kirklin, Ryan Cantor, Devin Koehl, Ashwin Lal, Peter Chau, Valerie Curren, Jonathan B Edelson, John J Parent, Hannah Victor, Ali Burnette, Jacqueline M Lamour
Journal: Journal of the American College of Cardiology (2024)
Effect of Cholesterol-Lowering Variants in ANGPTL3 and APOB Genes on Liver Disease
Authors: Alessia Di Costanzo, Ilaria Pirona, Silvia Buonaiuto, Laura D'Erasmo, Simone Bini, Daniele Tramontano, Stella Covino, Carlo Maiorca, Ilenia Minicocci, Marialuisa Sponziello, Francesco Baratta, Daniela Commodari, Vincenza Colonna, Allegra Via, Marcello Arca
Journal: Journal of the American College of Cardiology (2024)
Gal-3 blocks the binding between PD-1 and pembrolizumab
Authors: Stinne Ravn Greisen, Mia Bendix, Morten Aagaard Nielsen, Kathrine Pedersen, Nina Haunstrup Jensen, Malene Hvid, Jakob Hauge Mikkelsen, Taner Drace, Thomas Boesen, Torben Steiniche, Henrik Schmidt, Bent Deleuran
Journal: Journal for ImmunoTherapy of Cancer (2024)

Introduction Immune checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic malignant melanoma (MM) and improved long-term survival. Despite the impressive results, some patients still have progressive disease, and the search for biomarkers predicting response to ICI treatment is ongoing. In this search, galectin-3 (Gal-3) has been suggested as a molecule of interest, both as a marker of treatment response and as a treatment target to potentiate ICI therapy. We have previously demonstrated the binding between programmed cell death 1 (PD-1) and Gal-3, and here, we investigated the interaction between PD-1, pembrolizumab, and Gal-3 in metastatic MM patients. Methods The binding between PD-1, pembrolizumab and Gal-3 was investigated by surface plasmon resonance (SPR) and cryogenic electron microscopy (cryo-EM). The function was studied in in vitro cultures and soluble levels of both PD-1 and Gal-3 were measured in metastatic MM patients, treated with pembrolizumab. Results By SPR, we demonstrated that Gal-3 can block the binding between PD-1 and pembrolizumab, and further visualized a steric inhibition using cryo-EM. T cells cultured with Gal-3 had reduced pro-inflammatory cytokine production, which could not be rescued by pembrolizumab. In patients with metastatic MM, high levels of Gal-3 in plasma were found in patients with a longer progression-free survival in the study period, whereas high Gal-3 expression in the tumor was seen in patients with disease progression. Soluble PD-1 levels in plasma increased after treatment with pembrolizumab and correlated with disease progression. Conclusion We demonstrate that the interaction between PD-1 and Gal-3 interferes with the binding of pembrolizumab, supporting that an immune suppression induced by Gal-3 in the tumor microenvironment cannot be rescued by pembrolizumab.
Cancer cell-specific PD-L1 expression is a predictor of poor outcome in patients with locally advanced oral cavity squamous cell carcinoma
Authors: Minyu Wang, Lei Qin, Kevin Thia, Thu Nguyen, Sean MacDonald, Simone Belobrov, Sevastjan Kranz, David Goode, Joseph A Trapani, David Wiesenfeld, Paul Joseph Neeson
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Locally advanced oral cavity squamous cell carcinoma (OCSCC) presents a significant clinical challenge despite being partially responsive to standard treatment modalities. This study investigates the prognostic implications of programmed death-ligand 1 (PD-L1) expression in these tumors, focusing on its association with treatment outcomes and the immune microenvironment. Methods We assessed tumor-infiltrating lymphocytes (TILs) in 132 patients with OCSCC to evaluate their impact on survival. Multiplex immunohistochemistry staining for CD3, CD68, CD11c, PD-L1, and P40 was used to explore correlations with clinical outcomes in patients with early-stage (n=22) and locally advanced (n=36) OCSCC. These initial findings were validated through differential gene expression analysis, gene set enrichment, and immune cell deconvolution in a The Cancer Genome Atlas cohort of 163 locally advanced OCSCC tumors. Additionally, single-cell RNA sequencing (scRNA-seq) on a smaller cohort (n=10) further characterized the PD-L1 hi or PD-L1 lo cancer cells in these tumors. Results Elevated PD-L1 expression was associated with poor outcomes in patients with locally advanced OCSCC undergoing standard adjuvant therapy, irrespective of “hot” or “cold” classification based on TILs assessment. PD-L1 hi tumors exhibited an active immune response phenotype, enriched with M1 macrophages, CD8 + T cells and T regulatory cells in the tumor microenvironment. Notably, the negative impact of PD-L1 expression on outcomes was primarily attributed to its expression by cancer cells, rather than immune cells. Furthermore, scRNA-seq revealed that immune interactions were not essential for PD-L1 upregulation in cancer cells, instead, complex regulatory networks were involved. Additionally, PD-L1 lo locally advanced tumors exhibited more complex pathway enrichment and diverse T-cell populations compared with those in the early-stage. Conclusion Our findings underscore the prognostic significance of PD-L1 expression in locally advanced OCSCC, and unveil the complex interplay between PD-L1 expression, immune responses, and molecular pathways in the tumor microenvironment. This study provides insights that may inform future therapeutic strategies, including the possibility of tailored immunotherapeutic approaches for patients with PD-L1 hi locally advanced OCSCC.
Novel bispecific antibody-drug conjugate targeting PD-L1 and B7-H3 enhances antitumor efficacy and promotes immune-mediated antitumor responses
Authors: Yijun Dong, Zongliang Zhang, Siyuan Luan, Meijun Zheng, Zeng Wang, Yongdong Chen, Xiaoting Chen, Aiping Tong, Hui Yang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Antibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity.
Injectable double-crosslinked bone cement with enhanced bone adhesion and improved osteoporotic pathophysiological microenvironment for osteoregeneration in osteoporosis
Authors: Lingfei Zhao, Chenyu Liu, Xing Chen, Zirui He, Shuiquan Zhang, Anan Zhang, Shuaimin Tang, Zihan Wu, Changsheng Liu, Yuan Yuan
Journal: Bioactive Materials (2024)
Toward an understanding of collective intellectual humility
Authors: Elizabeth J Krumrei-Mancuso, Philip Pärnamets, Steven Bland, Mandi Astola, Aleksandra Cichocka, Jeroen de Ridder, Hugo Mercier, Marco Meyer, Cailin O'Connor, Tenelle Porter, Alessandra Tanesini, Mark Alfano, Jay J Van Bavel
Journal: Trends in Cognitive Sciences (2024)
Cellular taxonomy of the preleukemic bone marrow niche of acute myeloid leukemia
Authors: Chinmayee Goda, Rohan Kulkarni, Yaphet Bustos, Wenjun Li, Alexander Rudich, Ozlen Balcioglu, Sadie Chidester, Amog P Urs, Malith Karunasiri, Yzen Al-Marrawi, Erin Korn, Sanjay Kanna, Elizabeth A R Garfinkle, Nisarg Shah, Ashley Wooten, Bethany Mundy-Bosse, Lalit Sehgal, Bin Zhang, Guido Marcucci, Elaine R Mardis, Ramiro Garzon, Robert L Bowman, Aaron D Viny, Linde A Miles, Katherine E Miller, Adrienne M Dorrance
Journal: Leukemia (2024)
Radiofrequency ablation: mechanisms and clinical applications
Authors: Jianhua Wu, Zhiyuan Zhou, Yuanwen Huang, Xinyue Deng, Siting Zheng, Shangwen He, Genjie Huang, Binghui Hu, Min Shi, Wangjun Liao, Na Huang
Journal: MedComm (2024)

Abstract Radiofrequency ablation (RFA), a form of thermal ablation, employs localized heat to induce protein denaturation in tissue cells, resulting in cell death. It has emerged as a viable treatment option for patients who are ineligible for surgery in various diseases, particularly liver cancer and other tumor‐related conditions. In addition to directly eliminating tumor cells, RFA also induces alterations in the infiltrating cells within the tumor microenvironment (TME), which can significantly impact treatment outcomes. Moreover, incomplete RFA (iRFA) may lead to tumor recurrence and metastasis. The current challenge is to enhance the efficacy of RFA by elucidating its underlying mechanisms. This review discusses the clinical applications of RFA in treating various diseases and the mechanisms that contribute to the survival and invasion of tumor cells following iRFA, including the roles of heat shock proteins, hypoxia, and autophagy. Additionally, we analyze‌ the changes occurring in infiltrating cells within the TME after iRFA. Finally, we provide a comprehensive summary of clinical trials involving RFA in conjunction with other treatment modalities in the field of cancer therapy, aiming to offer novel insights and references for improving the effectiveness of RFA.
GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity
Authors: Jiaxian Yan, Chi Zhang, Yueli Xu, Zonghui Huang, Qingyuan Ye, Xiaojun Qian, Liang Zhu, Guangming Huang, Xiaqiong Wang, Wei Jiang, Rongbin Zhou
Journal: Nature Immunology (2024)
MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution
Authors: Clare Puttick, Thomas P Jones, Michelle M Leung, Felipe Galvez-Cancino, Jiali Liu, Manuel Varas-Godoy, Andrew Rowan, Oriol Pich, Carlos Martinez-Ruiz, Robert Bentham, Krijn K Dijkstra, James R M Black, Rachel Rosenthal, Nnennaya Kanu, Kevin Litchfield, Roberto Salgado, David A Moore, Peter Van Loo, Mariam Jamal-Hanjani, Sergio A Quezada, Charles Swanton, Nicholas McGranahan
Journal: Nature Genetics (2024)

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% and 15% of LUAD, LUSC and ER+ cancers. Consistent with the importance of HLA dysfunction in tumor evolution, in LUADs, HLA LOH was associated with metastasis and LUAD primary tumor regions seeding a metastasis had a lower effective neoantigen burden than non-seeding regions. These data highlight the extent and importance of HLA transcriptomic disruption, including repression and alternative splicing in cancer evolution.
Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa
Authors: Rohini Janivara, Wenlong C Chen, Ujani Hazra, Shakuntala Baichoo, Ilir Agalliu, Paidamoyo Kachambwa, Corrine N Simonti, Lyda M Brown, Saanika P Tambe, Michelle S Kim, Maxine Harlemon, Mohamed Jalloh, Dillon Muzondiwa, Daphne Naidoo, Olabode O Ajayi, Nana Yaa Snyper, Lamine Niang, Halimatou Diop, Medina Ndoye, James E Mensah, Afua O D Abrahams, Richard Biritwum, Andrew A Adjei, Akindele O Adebiyi, Olayiwola Shittu, Olufemi Ogunbiyi, Sikiru Adebayo, Maxwell M Nwegbu, Hafees O Ajibola, Olabode P Oluwole, Mustapha A Jamda, Audrey Pentz, Christopher A Haiman, Petrus V Spies, André van der Merwe, Michael B Cook, Stephen J Chanock, Sonja I Berndt, Stephen Watya, Alexander Lubwama, Mazvita Muchengeti, Sean Doherty, Natalie Smyth, David Lounsbury, Brian Fortier, Thomas E Rohan, Judith S Jacobson, Alfred I Neugut, Ann W Hsing, Alexander Gusev, Oseremen I Aisuodionoe-Shadrach, Maureen Joffe, Ben Adusei, Serigne M Gueye, Pedro W Fernandez, Jo McBride, Caroline Andrews, Lindsay N Petersen, Joseph Lachance, Timothy R Rebbeck
Journal: Nature Genetics (2024)
<i>LRP1</i> Repression by SNAIL Results in ECM Remodeling in Genetic Risk for Vascular Diseases
Authors: Lu Liu, Joséphine Henry, Yingwei Liu, Charlène Jouve, Jean-Sébastien Hulot, Adrien Georges, Nabila Bouatia-Naji
Journal: Circulation Research (2024)

BACKGROUND: Genome-wide association studies implicate common genetic variations in the LRP1 (low-density lipoprotein receptor-related protein 1) locus at risk for multiple vascular diseases and traits. However, the underlying biological mechanisms are unknown. METHODS: Fine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent stem cells were genome-edited using CRISPR-Cas9 to delete or modify candidate enhancer regions and generate LRP1 knockout cell lines. Cells were differentiated into smooth muscle cells through a mesodermal lineage. Transcription regulation was assessed using luciferase reporter assay, transcription factor knockdown, and chromatin immunoprecipitation. Phenotype changes in cells were conducted using cellular assays, bulk RNA sequencing, and mass spectrometry. RESULTS: Multitrait colocalization analyses pointed at rs11172113 as the most likely causal variant in LRP1 for fibromuscular dysplasia, migraine, pulse pressure, and pulmonary function trait. We found the rs11172113-T allele to associate with higher LRP1 expression. Genomic deletion in induced pluripotent stem cell–derived smooth muscle cells supported rs11172113 to locate in an enhancer region regulating LRP1 expression. We found transcription factors MECP2 (methyl CpG binding protein 2) and SNAIL to repress LRP1 expression through an allele-specific mechanism, involving SNAIL interaction with disease risk allele. LRP1 knockout decreased induced pluripotent stem cell–derived smooth muscle cell proliferation and migration. Differentially expressed genes were enriched for collagen-containing extracellular matrix, connective tissue development, and lung development. LRP1 knockout and deletion of rs11172113 enhancer showed potentiated canonical TGF-β (transforming growth factor beta) signaling through enhanced phosphorylation of SMAD2/3. Analyses of the protein content of decellularized extracts indicated partial extracellular matrix remodeling involving enhanced secretion of CYR61, a known LRP1 ligand involved in vascular integrity and TIMP3, implicated in extracellular matrix maintenance and also known to interact with LRP1. CONCLUSIONS: Our findings support allele-specific LRP1 gene repression by the endothelial-to-mesenchymal transition regulator SNAIL. We propose decreased LRP1 expression in smooth muscle cells to remodel the extracellular matrix enhanced by TGF-β as a potential mechanism of this pleiotropic locus for vascular diseases.
Roles of X-box binding protein 1 in liver pathogenesis
Authors: Jihoon Tak, Yun Seok Kim, Sang Geon Kim
Journal: Clinical and Molecular Hepatology (2024)

The prevalence of drug-induced liver injury (DILI) and viral liver infections presents significant challenges in modern healthcare and contributes to considerable morbidity and mortality worldwide. Concurrently, metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a major public health concern, reflecting the increasing rates of obesity and leading to more severe complications such as fibrosis and hepatocellular carcinoma. X-box binding protein 1 (XBP1) is a distinct transcription factor with a basic-region leucine zipper structure, whose activity is regulated by alternative splicing in response to disruptions in endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR) activation. XBP1 interacts with a key signaling component of the highly conserved UPR and is critical in determining cell fate when responding to ER stress in liver diseases. This review aims to elucidate the emerging roles and molecular mechanisms of XBP1 in liver pathogenesis, focusing on its involvement in DILI, viral liver infections, MAFLD, fibrosis/cirrhosis, and liver cancer. Understanding the multifaceted functions of XBP1 in these liver diseases offers insights into potential therapeutic strategies to restore ER homeostasis and mitigate liver damage.
Essential Role of the RIα Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development
Authors: Ibrahim Bedioune, Marine Gandon-Renard, Matthieu Dessillons, Aurélien Barthou, Audrey Varin, Delphine Mika, Saïd Bichali, Joffrey Cellier, Patrick Lechène, Sarah Karam, Maya Dia, Susana Gomez, Walma Pereira de Vasconcelos, Françoise Mercier-Nomé, Philippe Mateo, Audrey Dubourg, Constantine A. Stratakis, Jean-Jacques Mercadier, Jean-Pierre Benitah, Vincent Algalarrondo, Jérôme Leroy, Rodolphe Fischmeister, Ana-Maria Gomez, Grégoire Vandecasteele
Journal: Circulation (2024)

BACKGROUND: The heart expresses 2 main subtypes of cAMP-dependent protein kinase (PKA; type I and II) that differ in their regulatory subunits, RIα and RIIα. Embryonic lethality of RIα knockout mice limits the current understanding of type I PKA function in the myocardium. The objective of this study was to test the role of RIα in adult heart contractility and pathological remodeling. METHODS: We measured PKA subunit expression in human heart and developed a conditional mouse model with cardiomyocyte-specific knockout of RIα (RIα-icKO). Myocardial structure and function were evaluated by echocardiography, histology, and ECG and in Langendorff-perfused hearts. PKA activity and cAMP levels were determined by immunoassay, and phosphorylation of PKA targets was assessed by Western blot. L-type Ca 2+ current ( I Ca,L ), sarcomere shortening, Ca 2+ transients, Ca 2+ sparks and waves, and subcellular cAMP were recorded in isolated ventricular myocytes (VMs). RESULTS: RIα protein was decreased by 50% in failing human heart with ischemic cardiomyopathy and by 75% in the ventricles and in VMs from RIα-icKO mice but not in atria or sinoatrial node. Basal PKA activity was increased ≈3-fold in RIα-icKO VMs. In young RIα-icKO mice, left ventricular ejection fraction was increased and the negative inotropic effect of propranolol was prevented, whereas heart rate and the negative chronotropic effect of propranolol were not modified. Phosphorylation of phospholamban, ryanodine receptor, troponin I, and cardiac myosin-binding protein C at PKA sites was increased in propranolol-treated RIα-icKO mice. Hearts from RIα-icKO mice were hypercontractile, associated with increased I Ca,L, and [Ca 2+ ] i transients and sarcomere shortening in VMs. These effects were suppressed by the PKA inhibitor, H89. Global cAMP content was decreased in RIα-icKO hearts, whereas local cAMP at the phospholamban/sarcoplasmic reticulum Ca 2+ ATPase complex was unchanged in RIα-icKO VMs. RIα-icKO VMs had an increased frequency of Ca 2+ sparks and proarrhythmic Ca 2+ waves, and RIα-icKO mice had an increased susceptibility to ventricular tachycardia. On aging, RIα-icKO mice showed progressive contractile dysfunction, cardiac hypertrophy, and fibrosis, culminating in congestive heart failure with reduced ejection fraction that caused 50% mortality at 1 year. CONCLUSIONS: These results identify RIα as a key negative regulator of cardiac contractile function, arrhythmia, and pathological remodeling.
Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis
Authors: Davor Vukadinović, Lucas Lauder, David E. Kandzari, Deepak L. Bhatt, Ajay J. Kirtane, Elazer R. Edelman, Roland E. Schmieder, Michel Azizi, Michael Böhm, Felix Mahfoud
Journal: Circulation (2024)

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension.
Sinusoidal communication in chronic liver disease
Authors: Albert Gibert-Ramos, María Andrés-Rozas, Raül Pastó, Pablo Alfaro-Retamero, Sergi Guixé-Muntet, Jordi Gracia-Sancho
Journal: Clinical and Molecular Hepatology (2024)

The liver sinusoid, mainly composed of liver sinusoidal endothelial cells, hepatic macrophages and hepatic stellate cells, shapes the hepatic vasculature and is key maintaining liver homeostasis and function. During chronic liver disease (CLD), the function of sinusoidal cells is impaired, being directly involved in the progression of liver fibrosis, cirrhosis, and main clinical complications including portal hypertension and hepatocellular carcinoma. In addition to their roles in liver diseases pathobiology, sinusoidal cells' paracrine communication or cross-talk is being studied as a mechanism of disease but also as a remarkable target for treatment. The aim of this review is to gather current knowledge of intercellular signalling in the hepatic sinusoid during the progression of liver disease. We summarise studies developed in pre-clinical models of CLD, specially emphasizing those pathways characterized in human-based clinically relevant models. Finally, we describe pharmacological treatments targeting sinusoidal communication as promising options to treat CLD and its clinical complications.