Top

Journal of Translational Medicine

Published in:

Open Access 01-12-2024 | Primary Biliary Cholangitis | Research

Multi-omics approaches for drug-response characterization in primary biliary cholangitis and autoimmune hepatitis variant syndrome

Authors: Fan Yang, Leyu Zhou, Yi Shen, Xianglin Wang, Xiaoli Fan, Li Yang

Published in: Journal of Translational Medicine | Issue 1/2024

Abstract

Background

Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) variant syndrome (VS) exhibit a complex overlap of AIH features with PBC, leading to poorer prognoses than those with PBC or AIH alone. The biomarkers associated with drug response and potential molecular mechanisms in this syndrome have not been fully elucidated.

Methods

Whole-transcriptome sequencing was employed to discern differentially expressed (DE) RNAs within good responders (GR) and poor responders (PR) among patients with PBC/AIH VS. Subsequent gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for the identified DE RNAs. Plasma metabolomics was employed to delineate the metabolic profiles distinguishing PR and GR groups. The quantification of immune cell profiles and associated cytokines was achieved through flow cytometry and immunoassay technology. Uni- and multivariable logistic regression analyses were conducted to construct a predictive model for insufficient biochemical response. The performance of the model was assessed by computing the area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity.

Findings

The analysis identified 224 differentially expressed (DE) mRNAs, 189 DE long non-coding RNAs, 39 DE circular RNAs, and 63 DE microRNAs. Functional pathway analysis revealed enrichment in lipid metabolic pathways and immune response. Metabolomics disclosed dysregulated lipid metabolism and identified PC (18:2/18:2) and PC (16:0/20:3) as predictors. CD4⁺ T helper (Th) cells, including Th2 cells and regulatory T cells (Tregs), were upregulated in the GR group. Pro-inflammatory cytokines (IFN-γ, TNF-α, IL-9, and IL-17) were downregulated in the GR group, while anti-inflammatory cytokines (IL-10, IL-4, IL-5, and IL-22) were elevated. Regulatory networks were constructed, identifying CACNA1H and ACAA1 as target genes. A predictive model based on these indicators demonstrated an AUC of 0.986 in the primary cohort and an AUC of 0.940 in the validation cohort for predicting complete biochemical response.

Conclusion

A combined model integrating genomic, metabolic, and cytokinomic features demonstrated high accuracy in predicting insufficient biochemical response in patients with PBC/AIH VS. Early recognition of individuals at elevated risk for insufficient response allows for the prompt initiation of additional treatments.

Available only for authorised users

Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmmune hepatitis. Cell Mol Immunol. 2022;19:158–76. https://doi.org/10.1038/s41423-021-00768-8.CrossRefPubMed

Mieli-Vergani G, et al. Autoimmune hepatitis. Nat Rev Dis Primers. 2018;4:18017. https://doi.org/10.1038/nrdp.2018.17.CrossRefPubMed

Lleo A, Wang GQ, Gershwin ME, Hirschfield GM. Primary biliary cholangitis. Lancet. 2020;396:1915–26. https://doi.org/10.1016/S0140-6736(20)31607-X.CrossRefPubMed

Gulamhusein AF, Hirschfield GM. Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol. 2020;17:93–110. https://doi.org/10.1038/s41575-019-0226-7.CrossRefPubMed

Schultheiss C, et al. Immune signatures in variant syndromes of primary biliary cholangitis and autoimmune hepatitis. Hepatol Commun. 2023;7: e0123. https://doi.org/10.1097/HC9.0000000000000123.CrossRefPubMedPubMedCentral

Lee BT, et al. IgG:IgM ratios of liver plasma cells reveal similar phenotypes of primary biliary cholangitis with and without features of autoimmune hepatitis. Clin Gastroenterol Hepatol. 2021;19:397–9. https://doi.org/10.1016/j.cgh.2019.11.024.CrossRefPubMed

Schulz L, Sebode M, Weidemann SA, Lohse AW. Variant syndromes of primary biliary cholangitis. Best Pract Res Clin Gastroenterol. 2018;34–35:55–61. https://doi.org/10.1016/j.bpg.2018.06.003.CrossRefPubMed

Czaja AJ, Carpenter HA. Autoimmune hepatitis overlap syndromes and liver pathology. Gastroenterol Clin North Am. 2017;46:345–64. https://doi.org/10.1016/j.gtc.2017.01.008.CrossRefPubMed

Weiler-Normann C, Lohse AW. Variant syndromes of autoimmune liver diseases: classification, diagnosis and management. Dig Dis. 2016;34:334–9. https://doi.org/10.1159/000444472.CrossRefPubMed

10.

Chazouilleres O, et al. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology. 1998;28:296–301. https://doi.org/10.1002/hep.510280203.CrossRefPubMed

11.

Bonder A, Retana A, Winston DM, Leung J, Kaplan MM. Prevalence of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Clin Gastroenterol Hepatol. 2011;9:609–12. https://doi.org/10.1016/j.cgh.2011.03.019.CrossRefPubMed

12.

Zhang H, et al. Combination therapy of ursodeoxycholic acid and budesonide for PBC-AIH overlap syndrome: a meta-analysis. Drug Des Devel Ther. 2015;9:567–74. https://doi.org/10.2147/DDDT.S74515.CrossRefPubMedPubMedCentralADS

13.

Ozaslan E, et al. Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis. Clin Gastroenterol Hepatol. 2014;12:863–9. https://doi.org/10.1016/j.cgh.2013.09.021.CrossRefPubMed

14.

Muratori P, et al. The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Am J Gastroenterol. 2009;104:1420–5. https://doi.org/10.1038/ajg.2009.126.CrossRefPubMed

15.

Heurgue A, et al. Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis: a retrospective study of 115 cases of autoimmune liver disease. Gastroenterol Clin Biol. 2007;31:17–25. https://doi.org/10.1016/s0399-8320(07)89323-7.CrossRefPubMed

16.

Poupon R, Chazouilleres O, Corpechot C, Chretien Y. Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis. Hepatology. 2006;44:85–90. https://doi.org/10.1002/hep.21229.CrossRefPubMed

17.

Chazouilleres O, Wendum D, Serfaty L, Rosmorduc O, Poupon R. Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. J Hepatol. 2006;44:400–6. https://doi.org/10.1016/j.jhep.2005.10.017.CrossRefPubMed

18.

Jiang Y, Xu BH, Rodgers B, Pyrsopoulos N. Characteristics and inpatient outcomes of primary biliary cholangitis and autoimmune hepatitis overlap syndrome. J Clin Transl Hepatol. 2021;9:392–8. https://doi.org/10.14218/JCTH.2021.00008.CrossRefPubMedPubMedCentral

19.

Park Y, Cho Y, Cho EJ, Kim YJ. Retrospective analysis of autoimmune hepatitis-primary biliary cirrhosis overlap syndrome in Korea: characteristics, treatments, and outcomes. Clin Mol Hepatol. 2015;21:150–7. https://doi.org/10.3350/cmh.2015.21.2.150.CrossRefPubMedPubMedCentral

20.

Wen M, et al. Worse response to ursodeoxycholic acid in primary biliary cholangitis patients with autoimmune hepatitis features. Dig Dis. 2021;39:366–74. https://doi.org/10.1159/000513331.CrossRefPubMed

21.

Fan X, et al. Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome: a real-world study. Chin Med J (Engl). 2023;136:735–6. https://doi.org/10.1097/CM9.0000000000002261.CrossRefPubMed

22.

Sveinbjornsson G, et al. Multiomics study of nonalcoholic fatty liver disease. Nat Genet. 2022;54:1652–63. https://doi.org/10.1038/s41588-022-01199-5.CrossRefPubMedPubMedCentral

23.

Li K, et al. Whole-transcriptome sequencing revealed differentially expressed mRNAs and non-coding RNAs played crucial roles in NiONPs-induced liver fibrosis. Ecotoxicol Environ Saf. 2022;248: 114308. https://doi.org/10.1016/j.ecoenv.2022.114308.CrossRefPubMed

24.

Jiang Z, et al. Whole transcriptome analysis with sequencing: methods, challenges and potential solutions. Cell Mol Life Sci. 2015;72:3425–39. https://doi.org/10.1007/s00018-015-1934-y.CrossRefPubMedPubMedCentral

25.

de Correia Sousa M, Gjorgjieva M, Dolicka D, Sobolewski C, Foti M. Deciphering miRNAs’ action through miRNA editing. Int J Mol Sci. 2019;20:6249. https://doi.org/10.3390/ijms20246249.CrossRef

26.

Wu T, Du Y. LncRNAs: from basic research to medical application. Int J Biol Sci. 2017;13:295–307. https://doi.org/10.7150/ijbs.16968.CrossRefPubMedPubMedCentral

27.

Chen L, et al. The bioinformatics toolbox for circRNA discovery and analysis. Brief Bioinform. 2021;22:1706–28. https://doi.org/10.1093/bib/bbaa001.CrossRefPubMed

28.

Zhang L, et al. Comprehensive analysis of the competing endogenous circRNA-lncRNA-miRNA-mRNA network and identification of a novel potential biomarker for hepatocellular carcinoma. Aging (Albany NY). 2021;13:15990–6008. https://doi.org/10.18632/aging.203056.CrossRefPubMed

29.

Zeng Q, et al. LncRNA and circRNA in patients with non-alcoholic fatty liver disease: a systematic review. Biomolecules. 2023;13:560. https://doi.org/10.3390/biom13030560.CrossRefPubMedPubMedCentral

30.

Ahmed F, Samantasinghar A, Soomro AM, Kim S, Choi KH. A systematic review of computational approaches to understand cancer biology for informed drug repurposing. J Biomed Inform. 2023;142: 104373. https://doi.org/10.1016/j.jbi.2023.104373.CrossRefPubMed

31.

Ahmed F, et al. Drug repurposing in psoriasis, performed by reversal of disease-associated gene expression profiles. Comput Struct Biotechnol J. 2022;20:6097–107. https://doi.org/10.1016/j.csbj.2022.10.046.CrossRefPubMedPubMedCentral

32.

Zhou T, Ismail A, Francis H. Bile acids in autoimmune liver disease: unveiling the nexus of inflammation, inflammatory cells, and treatment strategies. Cells. 2023;12:2725. https://doi.org/10.3390/cells12232725.CrossRefPubMedPubMedCentral

33.

Wang JB, et al. Metabolomic profiling of autoimmune hepatitis: the diagnostic utility of nuclear magnetic resonance spectroscopy. J Proteome Res. 2014;13:3792–801. https://doi.org/10.1021/pr500462f.CrossRefPubMed

34.

Lafdil F, Miller AM, Ki SH, Gao B. Th17 cells and their associated cytokines in liver diseases. Cell Mol Immunol. 2010;7:250–4. https://doi.org/10.1038/cmi.2010.5.CrossRefPubMedPubMedCentral

35.

Akberova D, Kiassov AP, Abdulganieva D. Serum cytokine levels and their relation to clinical features in patients with autoimmune liver diseases. J Immunol Res. 2017;2017:9829436. https://doi.org/10.1155/2017/9829436.CrossRefPubMedPubMedCentral

36.

Ahmed F, et al. Drug repurposing for viral cancers: A paradigm of machine learning, deep learning, and virtual screening-based approaches. J Med Virol. 2023;95: e28693. https://doi.org/10.1002/jmv.28693.CrossRefPubMed

37.

Floreani A, et al. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol. 2005;100:1516–22. https://doi.org/10.1111/j.1572-0241.2005.41841.x.CrossRefPubMed

38.

European Association for the Study of the Liver. EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67:145–72. https://doi.org/10.1016/j.jhep.2017.03.022.CrossRef

39.

Li Y, et al. Identification and analysis of lncRNA, microRNA and mRNA expression profiles and construction of ceRNA network in Talaromyces marneffei-infected THP-1 macrophage. PeerJ. 2021;9: e10529. https://doi.org/10.7717/peerj.10529.CrossRefPubMedPubMedCentral

40.

An S, et al. Genome-wide profiling reveals alternative polyadenylation of innate immune-related mRNA in patients with COVID-19. Front Immunol. 2021;12: 756288. https://doi.org/10.3389/fimmu.2021.756288.CrossRefPubMedPubMedCentral

41.

Andersson D, et al. Properties of targeted preamplification in DNA and cDNA quantification. Expert Rev Mol Diagn. 2015;15:1085–100. https://doi.org/10.1586/14737159.2015.1057124.CrossRefPubMedPubMedCentral

42.

Dunn WB, et al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc. 2011;6:1060–83. https://doi.org/10.1038/nprot.2011.335.CrossRefPubMed

43.

Wen B, Mei Z, Zeng C, Liu S. metaX: a flexible and comprehensive software for processing metabolomics data. BMC Bioinformatics. 2017;18:183. https://doi.org/10.1186/s12859-017-1579-y.CrossRefPubMedPubMedCentral

44.

Boulesteix AL, Strimmer K. Partial least squares: a versatile tool for the analysis of high-dimensional genomic data. Brief Bioinform. 2007;8:32–44. https://doi.org/10.1093/bib/bbl016.CrossRefPubMed

45.

Haspel JA, et al. Circadian rhythm reprogramming during lung inflammation. Nat Commun. 2014;5:4753. https://doi.org/10.1038/ncomms5753.CrossRefPubMedADS

46.

Sreekumar A, et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009;457:910–4. https://doi.org/10.1038/nature07762.CrossRefPubMedPubMedCentralADS

47.

Guerrero D, et al. Evaluation of cutaneous immune response in a controlled human in vivo model of mosquito bites. Nat Commun. 2022;13:7036. https://doi.org/10.1038/s41467-022-34534-9.CrossRefPubMedPubMedCentralADS

48.

Ulmer AJ, Scholz W, Ernst M, Brandt E, Flad HD. Isolation and subfractionation of human peripheral blood mononuclear cells (PBMC) by density gradient centrifugation on Percoll. Immunobiology. 1984;166:238–50. https://doi.org/10.1016/S0171-2985(84)80042-X.CrossRefPubMed

49.

Holmes K, Lantz LM, Fowlkes BJ, Schmid I, Giorgi JV. Preparation of cells and reagents for flow cytometry. Curr Protoc Immunol. 2001. https://doi.org/10.1002/0471142735.im0503s44.CrossRefPubMed

50.

Reed J, Wetzel SA. CD4(+) T cell differentiation and activation. Methods Mol Biol. 1803;335–351:2018. https://doi.org/10.1007/978-1-4939-8549-4_20.CrossRef

51.

Sheng W, et al. Multiplex immunofluorescence: a powerful tool in cancer immunotherapy. Int J Mol Sci. 2023;24:3086. https://doi.org/10.3390/ijms24043086.CrossRefPubMedPubMedCentral

52.

Reshetnyak VI, Maev IV. Features of lipid metabolism disorders in primary biliary cholangitis. Biomedicines. 2022;10:3046. https://doi.org/10.3390/biomedicines10123046.CrossRefPubMedPubMedCentral

53.

Sirbe C, Simu G, Szabo I, Grama A, Pop TL. Pathogenesis of autoimmune hepatitis-cellular and molecular mechanisms. Int J Mol Sci. 2021;22:13578. https://doi.org/10.3390/ijms222413578.CrossRefPubMedPubMedCentral

54.

Chaplin DD. Overview of the immune response. J Allergy Clin Immunol. 2010;125:S3-23. https://doi.org/10.1016/j.jaci.2009.12.980.CrossRefPubMedPubMedCentral

55.

Mousset CM, et al. Comprehensive phenotyping of T cells using flow cytometry. Cytometry A. 2019;95:647–54. https://doi.org/10.1002/cyto.a.23724.CrossRefPubMed

56.

Montaldo E, et al. Human NK cell receptors/markers: a tool to analyze NK cell development, subsets and function. Cytometry A. 2013;83:702–13. https://doi.org/10.1002/cyto.a.22302.CrossRefPubMed

57.

Saravia J, Chapman NM, Chi H. Helper T cell differentiation. Cell Mol Immunol. 2019;16:634–43. https://doi.org/10.1038/s41423-019-0220-6.CrossRefPubMedPubMedCentral

58.

Dong C. Cytokine regulation and function in T Cells. Annu Rev Immunol. 2021;39:51–76. https://doi.org/10.1146/annurev-immunol-061020-053702.CrossRefPubMed

59.

Baven-Pronk AM, et al. The role of mycophenolate mofetil in the management of autoimmune hepatitis and overlap syndromes. Aliment Pharmacol Ther. 2011;34:335–43. https://doi.org/10.1111/j.1365-2036.2011.04727.x.CrossRefPubMed

60.

Wolf DC, Bojito L, Facciuto M, Lebovics E. Mycophenolate mofetil for autoimmune hepatitis: a single practice experience. Dig Dis Sci. 2009;54:2519–22. https://doi.org/10.1007/s10620-008-0632-0.CrossRefPubMed

61.

Stubbington MJ, et al. An atlas of mouse CD4(+) T cell transcriptomes. Biol Direct. 2015;10:14. https://doi.org/10.1186/s13062-015-0045-x.CrossRefPubMedPubMedCentral

62.

Robert V, et al. Protein kinase C-dependent activation of CaV1.2 channels selectively controls human TH2-lymphocyte functions. J Allergy Clin Immunol. 2014;133:1175–83. https://doi.org/10.1016/j.jaci.2013.10.038.CrossRefPubMed

63.

Wang H, et al. Low-voltage-activated CaV3.1 calcium channels shape T helper cell cytokine profiles. Immunity. 2016;44:782–94. https://doi.org/10.1016/j.immuni.2016.01.015.CrossRefPubMedPubMedCentral

64.

Wanders RJ, et al. Peroxisomal fatty acid alpha- and beta-oxidation in humans: enzymology, peroxisomal metabolite transporters and peroxisomal diseases. Biochem Soc Trans. 2001;29:250–67. https://doi.org/10.1042/0300-5127:0290250.CrossRefPubMed

65.

Wang Y, et al. Effect of the ACAA1 gene on preadipocyte differentiation in sheep. Front Genet. 2021;12: 649140. https://doi.org/10.3389/fgene.2021.649140.CrossRefPubMedPubMedCentral

66.

Zou RC, et al. Co-expression analysis and ceRNA network reveal eight novel potential lncRNA biomarkers in hepatocellular carcinoma. PeerJ. 2019;7: e8101. https://doi.org/10.7717/peerj.8101.CrossRefPubMedPubMedCentral

67.

Badmus OO, Hillhouse SA, Anderson CD, Hinds TD, Stec DE. Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways. Clin Sci (Lond). 2022;136:1347–66. https://doi.org/10.1042/CS20220572.CrossRefPubMed

68.

Mato JM, Alonso C, Noureddin M, Lu SC. Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease. World J Gastroenterol. 2019;25:3009–20. https://doi.org/10.3748/wjg.v25.i24.3009.CrossRefPubMedPubMedCentral

69.

Yang F, Fan X, Yang L. Dysregulation of the LPC-ATX-LPA axis in autoimmune hepatitis is associated with monocyte activation. J Hepatol. 2024;80:e14–6. https://doi.org/10.1016/j.jhep.2023.06.010.CrossRefPubMed

70.

Chaouali M, et al. High levels of proinflammatory cytokines IL-6, IL-8, TNF-Alpha, IL-23, and IFN- in Tunisian patients with type 1 autoimmune hepatitis. Eur Cytokine Netw. 2020. https://doi.org/10.1684/ecn.2020.0450.CrossRefPubMed

71.

Landi A, et al. Differential serum levels of eosinophilic eotaxins in primary sclerosing cholangitis, primary biliary cirrhosis, and autoimmune hepatitis. J Interferon Cytokine Res. 2014;34:204–14. https://doi.org/10.1089/jir.2013.0075.CrossRefPubMedPubMedCentral

72.

Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10:225–35. https://doi.org/10.1038/nri2735.CrossRefPubMedPubMedCentral

Title: Multi-omics approaches for drug-response characterization in primary biliary cholangitis and autoimmune hepatitis variant syndrome
Authors: Fan Yang
Leyu Zhou
Yi Shen
Xianglin Wang
Xiaoli Fan
Li Yang
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Primary Biliary Cholangitis
Autoimmune Hepatitis
Cytokines
Published in: Journal of Translational Medicine / Issue 1/2024
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-024-05029-6

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Findings

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2024

Multi-omics integration with weighted affinity and self-diffusion applied for cancer subtypes identification

Blockade of PI3K/AKT signaling pathway by Astragaloside IV attenuates ulcerative colitis via improving the intestinal epithelial barrier

Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter

CDSKNNXMBD: a novel clustering framework for large-scale single-cell data based on a stable graph structure

The microtubule targeting agent ST-401 triggers cell death in interphase and prevents the formation of polyploid giant cancer cells

Correction: Detecting the percent of peripheral blood mononuclear cells displaying p-STAT-3 in malignant glioma patients

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage