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    Original Article Open Access
    Protective Effect of Mesaconate on Autoimmune Hepatitis via Suppression of Inflammatory Response and Oxidative Stress
    Qian Zhang, Jiajun Wang, Yifan He, Kun Zhang, Wei Hong, Tao Han
    Journal of Clinical and Translational Hepatology, Published online July 18, 2025. doi:10.14218/JCTH.2025.00112
    Abstract
    Autoimmune hepatitis (AIH) is a severe immune-mediated liver disease with limited treatment options beyond immunosuppressants, which carry significant side effects. Existing evidence [...] Read more.

    Autoimmune hepatitis (AIH) is a severe immune-mediated liver disease with limited treatment options beyond immunosuppressants, which carry significant side effects. Existing evidence suggests that mesaconate (MSA) possesses immunomodulatory properties and may offer advantages over itaconate derivatives by avoiding succinate dehydrogenase inhibition. However, its specific role in AIH remains unclear. This study aimed to investigate the therapeutic effects of MSA on AIH and to elucidate its underlying mechanisms of action.

    A murine AIH model was established via tail vein injection of concanavalin A (ConA, 20 mg/kg). MSA (250 mg/kg) was administered intraperitoneally 6 h before ConA exposure. Liver histology, serum transaminase levels, apoptosis markers, oxidative stress markers, and inflammatory cytokines were analyzed to assess the therapeutic efficacy of MSA. Additionally, RNA sequencing and Western blotting were performed to explore the mechanisms of MSA action. In vitro validation was conducted using RAW264.7 macrophages pretreated with MSA (1 mM) followed by interferon-gamma (IFN-γ, 50 ng/mL) stimulation.

    MSA pretreatment effectively mitigated ConA-induced AIH by reducing inflammatory responses, oxidative stress, and apoptosis both in vivo and in vitro. The underlying protective mechanism involved MSA-mediated downregulation of IFN-γ expression and subsequent inhibition of the Janus tyrosine kinase 1/2–signal transducer and activator of transcription 1 signaling pathway. The involvement of this pathway in human AIH was also confirmed.

    This study provides the first evidence that MSA ameliorates AIH by suppressing the IFN-γ–Janus tyrosine kinase 1/2–signal transducer and activator of transcription 1 signaling pathway, offering novel mechanistic insights and a promising therapeutic candidate for the future treatment of autoimmune disorders.

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    Original Article Open Access
    Admission Albumin-Bilirubin Score Is Inferior to MELD, MELD-Na+ and Child-Turcotte-Pugh Score in Predicting Survival in Indian Patients with Alcohol-associated Liver Disease
    Chitta Ranjan Khatua, Prajna Anirvan, Manas Kumar Panigrahi, Shivaram Prasad Singh
    Journal of Translational Gastroenterology, Published online July 17, 2025. doi:10.14218/JTG.2025.00004
    Abstract
    Prognostic scores are valuable tools for predicting survival in patients with chronic liver disease. Recently, the albumin-bilirubin (ALBI) score has emerged as a potential prognostic [...] Read more.

    Prognostic scores are valuable tools for predicting survival in patients with chronic liver disease. Recently, the albumin-bilirubin (ALBI) score has emerged as a potential prognostic indicator in liver-related conditions. This study aimed to compare the prognostic efficacy of the ALBI score with the Model for End-stage Liver Disease (MELD), MELD-Na+, and Child-Turcotte-Pugh (CTP) scores in predicting survival among patients with alcohol-associated liver disease (ALD).

    This study included consecutive ALD patients admitted to the Medicine and Gastroenterology wards of MKCG Medical College and Hospital, Berhampur, Odisha, India, between November 2019 and November 2022. Upon hospitalization, baseline characteristics, clinical and laboratory parameters, ALBI, MELD, MELD-Na+, and CTP scores were recorded. The accuracy of these scores in predicting survival up to three years was compared.

    A total of 490 ALD patients were included. Higher ALBI scores were observed in patients who died during hospitalization (p < 0.001), at 28 days (p < 0.001), 90 days (p < 0.001), six months (p < 0.001), one year (p < 0.001), two years (p < 0.001), and three years (p < 0.001), compared to those who survived. However, the area under the receiver operating characteristic (AUROC) curves showed that the ALBI score was inferior to MELD, MELD-Na+, and CTP scores in predicting survival at admission [AUROC: ALBI (0.719), MELD-Na+ (0.823), MELD (0.817), CTP (0.770)] and at three years [AUROC: ALBI (0.755), MELD-Na+ (0.787), MELD (0.758), CTP (0.784)]. Furthermore, Cox regression analysis revealed that components used in the MELD, MELD-Na+, and CTP scores—such as serum creatinine, serum sodium, and hepatic encephalopathy—were independent predictors of mortality, whereas the components of the ALBI score (serum albumin and serum bilirubin) were not.

    All hospitalized ALD patients had a grade 3 ALBI score, with significantly higher scores observed among non-survivors compared to survivors. However, MELD, MELD-Na+, and CTP scores were superior to the ALBI score in predicting survival both during hospitalization and over a three-year follow-up period.

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    Original Article Open Access
    Biomarker Discovery for Metabolic Dysfunction-associated Steatotic Liver Disease Utilizing Mendelian Randomization, Machine Learning, and External Validation
    Gong Feng, Giovanni Targher, Christopher D. Byrne, Na He, Man Mi, Yi Liu, Hongbin Zhu, Ming-Hua Zheng, Feng Ye
    Journal of Clinical and Translational Hepatology, Published online July 16, 2025. doi:10.14218/JCTH.2025.00270
    Abstract
    The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers [...] Read more.

    The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers for MASLD and evaluate their diagnostic and prognostic significance.

    We conducted a Mendelian randomization analysis to assess the causal effects of 2,925 molecular biomarkers (from proteomics data) and 35 clinical biomarkers on MASLD. Mediation analysis was performed to determine whether clinical biomarkers mediated the effects of molecular biomarkers. The association between key clinical biomarkers and MASLD was externally validated in a hospital-based cohort (n = 415). A machine learning–based diagnostic model for MASLD was developed and validated using the identified molecular biomarkers. Prognostic significance was evaluated for both molecular and clinical biomarkers.

    Six molecular biomarkers—including canopy FGF signaling regulator 4 (CNPY4), ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6), and major histocompatibility complex, class I, A (HLA-A)—and eight clinical biomarkers (e.g., serum total protein (STP)) were identified as causally related to MASLD. STP partially mediated the effect of HLA-A on MASLD (23.61%) and was associated with MASLD in the external cohort (odds ratio = 1.080, 95% confidence interval: 1.011–1.155). A random forest model demonstrated high diagnostic performance (AUC = 0.941 in training; 0.875 in validation). High expression levels of CNPY4 and ENTPD6 were associated with the development of and poorer survival from hepatocellular carcinoma. Low STP (<60 g/L) predicted all-cause mortality (HR = 2.50, 95% confidence interval: 1.22–5.09).

    This study identifies six causal molecular biomarkers (e.g., CNPY4, ENTPD6, HLA-A) and eight clinical biomarkers for MASLD. Notably, STP mediates the effect of HLA-A on MASLD and is associated with all-cause mortality.

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    Review Article Open Access
    Environmental Triggers’ Involvement in the Development of Type 1 Diabetes Mellitus
    Tajudeen Olanrewaju Yahaya, Umar Usman Liman, Caleb Dikko Obadiah, Zafira Illo Zakari, Daniel Anyebe, Boniface Gomo Clement, Balkisu Marafa Muhammad
    Exploratory Research and Hypothesis in Medicine, Published online July 27, 2022. doi:10.14218/ERHM.2022.00051
    Abstract
    The huge burden of type 1 diabetes mellitus (T1DM) has been a source of concern globally since the Industrial Revolution in the 18th–19th centuries. To this end, studies have shown [...] Read more.

    The huge burden of type 1 diabetes mellitus (T1DM) has been a source of concern globally since the Industrial Revolution in the 18th–19th centuries. To this end, studies have shown that certain environmental changes that accompanied the Revolution may have increased the risk and burden of the disease in genetically predisposed individuals. However, documented studies that synthesize these environmental triggers are scarce. As a result, the current study was conceived to synthesize the environmental triggers of T1DM to boost public awareness. Relevant information was retrieved from reputable academic databases; namely, Scopus, PubMed, SpringerLink, and Embase. The results showed that chemical exposure, viral infection, gut microbiome disruption, vitamin and mineral deficiencies, inadequate or exclusive breastfeeding, as well as early exposure to infant feeding formulas could increase the risk and burden of T1DM in genetically predisposed individuals. As a consequence, these triggers could compromise the expression of certain genes involved in insulin synthesis and immune function, such as the human leukocyte antigen (HLA), insulin (INS), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and protein tyrosine phosphatase non-receptor type 22 (PTPN22) genes. This would result in a dysfunctional immune system in which immune cells, such as T-cells and B-cells and molecules, such as cytokines would attack self-tissues, thus causing autoimmunity of the pancreatic beta cells. Environmental triggers could also induce the T1DM pathophysiology by modifying the epigenome of the mentioned genes. Furthermore, some epigenetic changes could be reversed, which would infer that treatment procedures that would include the pathophysiology of the environmental triggers could be more effective.

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    Original Article Open Access
    Overexpression of RBM34 Promotes Tumor Progression and Correlates with Poor Prognosis of Hepatocellular Carcinoma
    Wei Wang, Rui Zhang, Ning Feng, Longzhen Zhang, Nianli Liu
    Journal of Clinical and Translational Hepatology, Published online July 13, 2022. doi:10.14218/JCTH.2022.00166
    Abstract
    Emerging evidence suggests that RNA-binding motif (RBM) proteins are involved in hepatocarcinogenesis and act either as oncogenes or tumor suppressors. The objective of this study [...] Read more.

    Emerging evidence suggests that RNA-binding motif (RBM) proteins are involved in hepatocarcinogenesis and act either as oncogenes or tumor suppressors. The objective of this study was to investigate the role of RBM34, an RBM protein, in hepatocellular carcinoma (HCC).

    We first examined the expression of RBM34 across cancers. The correlation of RBM34 with clinicopathological features and the prognostic value of RBM34 for HCC was then investigated. Functional enrichment analysis of RBM34-related differentially expressed genes (DEGs) was performed to explore its biological function. RNA sequencing (RNA-seq) was applied to identify downstream genes and pathways affected upon RBM34 knockout. The correlation of RBM34 with immune characteristics was also analyzed. The oncogenic function of RBM34 was examined in in vitro and in vivo experiments.

    RBM34 was highly expressed in hepatocellular carcinoma and correlated with poor clinicopathological features and prognosis. RBM34 was positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. A positive correlation was also observed between RBM34, T cell exhaustion, and regulatory T cell marker genes. Knockout of RBM34 significantly inhibited cell proliferation, migration, and xenograft tumor growth, and sensitized HCC cells to sorafenib treatment. RBM34 inhibition reduced FGFR2 expression and affected PI3K-AKT pathway activation in HCC cells.

    Our study suggests that RBM34 may serve as a new prognostic marker and therapeutic target of HCC.

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    Original Article Open Access
    Naringenin is a Potential Immunomodulator for Inhibiting Liver Fibrosis by Inhibiting the cGAS-STING Pathway
    Li Chen, Siwei Xia, Shuqi Wang, Yuanyuan Zhou, Feixia Wang, Zhanghao Li, Yang Li, Desong Kong, Zili Zhang, Jiangjuan Shao, Xuefen Xu, Feng Zhang, Shizhong Zheng
    Journal of Clinical and Translational Hepatology, Published online April 28, 2022. doi:10.14218/JCTH.2022.00120
    Abstract
    Naringenin is an anti-inflammatory flavonoid that has been studied in chronic liver disease. The mechanism specific to its antifibrosis activity needs further investigation This [...] Read more.

    Naringenin is an anti-inflammatory flavonoid that has been studied in chronic liver disease. The mechanism specific to its antifibrosis activity needs further investigation This study was to focused on the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) pathway in hepatic stellate cells and clarified the antifibrosis mechanism of naringenin.

    The relationship between the cGAS-stimulator of interferon genes (STING) pathway and liver fibrosis was analyzed using the Gene Expression Omnibus database. Histopathology, immunohistochemistry, fluorescence staining, Western blotting and polymerase chain reaction were performed to assess gene and protein expression levels associated with the cGAS pathway in clinical liver tissue samples and mouse livers. Molecular docking was performed to evaluate the relationship between naringenin and cGAS, and western blotting was performed to study the expression of inflammatory factors downstream of cGAS in vitro.

    Clinical database analyses showed that the cGAS-STING pathway is involved in the occurrence of chronic liver disease. Naringenin ameliorated liver injury and liver fibrosis, decreased collagen deposition and cGAS expression, and inhibited inflammation in carbon tetrachloride (CCl4)-treated mice. Molecular docking found that cGAS may be a direct target of naringenin. Consistent with the in vivo results, we verified the inhibitory effect of naringenin on activated hepatic stellate cells (HSCs). By using the cGAS-specific agonist double-stranded (ds)DNA, we showed that naringenin attenuated the activation of cGAS and its inflammatory factors affected by dsDNA. We verified that naringenin inhibited the cGAS-STING pathway, thereby reducing the secretion of inflammatory factors by HSCs to ameliorate liver fibrosis.

    Interrupting the cGAS-STING pathway helped reverse the fibrosis process. Naringenin has potential as an antihepatic fibrosis drug.

    Full article
Special Features

Call for Papers for Special Issue 'Updates of Cytopathology Reporting Systems'

Journal: Journal of Clinical and Translational Pathology
Special Issue: Updates of Cytopathology Reporting Systems
Submission deadline: November 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue 'Frontier research on the toxicity and efficacy of Chinese medicine'

Journal: Future Integrative Medicine
Special Issue: Frontier research on the toxicity and efficacy of Chinese medicine
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘New Translational Challenges in Primary Biliary Cholangitis’

Journal: Journal Clinical and Translational Hepatology
Special Issue: New Translational Challenges in Primary Biliary Cholangitis
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘A Spotlight on Progress and Pitfalls in NAFLD/MAFLD Studies, 2022’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: A Spotlight on Progress and Pitfalls in NAFLD/MAFLD Studies, 2022
Submission deadline: March 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue 'Comparative study of traditional medicine in the world'

Journal: Future Integrative Medicine
Special Issue: Comparative study of traditional medicine in the world
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue 'Therapeutic effects of herbal medicines on neurological impairment and related mental disorders based on the evidence of clinical and basic studies'

Journal: Future Integrative Medicine
Special Issue: Therapeutic effects of herbal medicines on neurological impairment and related mental disorders based on the evidence of clinical and basic studies
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Immunoregulatory Mechanisms of Herbal Medicines in Cancer and Infectious Diseases’

Journal: Future Integrative Medicine
Special Issue: Immunoregulatory Mechanisms of Herbal Medicines in Cancer and Infectious Diseases
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted
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