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    Research Letter Open Access
    TDF Promotes Glycolysis and Mitochondrial Dysfunction to Accelerate Lactate Accumulation by Downregulating PGC1α in Mice
    Yuxuan Luo, Zhiwei Chen, Zhao Li, Aoran Luo, Yi Zeng, Min Chen, Mingli Peng, Hong Ren, Peng Hu
    Journal of Clinical and Translational Hepatology, Published online February 3, 2023. doi:10.14218/JCTH.2022.00082
    Review Article Open Access
    Primary Non-HFE Hemochromatosis: A Review
    Alla Turshudzhyan, David C. Wu, George Y. Wu
    Journal of Clinical and Translational Hepatology, Published online February 2, 2023. doi:10.14218/JCTH.2022.00373
    Abstract
    Iron homeostasis is a complex process in which iron uptake and use are tightly balanced. Primary Type 1 or HFE hemochromatosis results from homozygous mutations in the gene that encodes [...] Read more.
    Iron homeostasis is a complex process in which iron uptake and use are tightly balanced. Primary Type 1 or HFE hemochromatosis results from homozygous mutations in the gene that encodes human homeostatic iron regulator (known as human factors engineering, HFE) protein, a regulator of hepcidin, and makes up approximately 90% of all hemochromatosis cases. However, four types of hemochromatosis do not involve the HFE gene. They are non-HFE hemochromatosis type 2A (HFE2, encoding HJV), type 2B (HAMP, encoding hepcidin), type 3 (TFR2, encoding transferring receptor-2), and types 4A and B (SLC40A1, encoding ferroportin. Non-HFE hemochromatosis is extremely rare. Pathogenic allele frequencies have been estimated to be 74/100,000 for type 2A, 20/100,000 for type 2B, 30/100,000 for type 3, and 90/100,000 for type 4 hemochromatosis. Current guidelines recommend that the diagnosis be made by ruling out HFE mutations, history, physical examination, laboratory values (ferritin and transferrin saturation), magnetic resonance or other imaging, and liver biopsy if needed. While less common, non-HFE hemochromatosis can cause iron overload as severe as the HFE type. In most cases, treatment involves phlebotomy and is successful if started before irreversible damage occurs. Early diagnosis and treatment are important because it prevents chronic liver disease. This review updates the mutations and their pathogenetic consequences, the clinical picture, diagnostic guidelines, and treatment of hemochromatosis. Full article
    Original Article Open Access
    Breath Biopsy® to Identify Exhaled Volatile Organic Compounds Biomarkers for Liver Cirrhosis Detection
    Giuseppe Ferrandino, Giovanna De Palo, Antonio Murgia, Owen Birch, Ahmed Tawfike, Rob Smith, Irene Debiram-Beecham, Olga Gandelman, Graham Kibble, Anne Marie Lydon, Alice Groves, Agnieszka Smolinska, Max Allsworth, Billy Boyle, Marc P. van der Schee, Michael Allison, Rebecca C. Fitzgerald, Matthew Hoare, Victoria K. Snowdon
    Journal of Clinical and Translational Hepatology, Published online February 2, 2023. doi:10.14218/JCTH.2022.00309
    Abstract
    The prevalence of chronic liver disease in adults exceeds 30% in some countries and there is significant interest in developing tests and treatments to help control disease progression [...] Read more.
    The prevalence of chronic liver disease in adults exceeds 30% in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare burden. Breath is a rich sampling matrix that offers non-invasive solutions suitable for early-stage detection and disease monitoring. Having previously investigated targeted analysis of a single biomarker, here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical use. To identify candidate biomarkers we compared 46 breath samples from cirrhosis patients and 42 from controls. Collection and analysis used Breath Biopsy OMNI™, maximizing signal and contrast to background to provide high confidence biomarker detection based upon gas chromatography mass spectrometry (GC-MS). Blank samples were also analyzed to provide detailed information on background volatile organic compounds (VOCs) levels. A set of 29 breath VOCs differed significantly between cirrhosis and controls. A classification model based on these VOCs had an area under the curve (AUC) of 0.95±0.04 in cross-validated test sets. The seven best performing VOCs were sufficient to maximize classification performance. A subset of 11 VOCs was correlated with blood metrics of liver function (bilirubin, albumin, prothrombin time) and separated patients by cirrhosis severity using principal component analysis. A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and monitoring, showing correlation to disease severity and serum biomarkers at late stage. Full article
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    Review Article Open Access
    Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options: An Update
    Kristina Duspara, Kristina Bojanic, Josipa Ivanusic Pejic, Lucija Kuna, Tea Omanovic Kolaric, Vjera Nincevic, Robert Smolic, Aleksandar Vcev, Marija Glasnovic, Ines Bilic Curcic, Martina Smolic
    Journal of Clinical and Translational Hepatology, Published online September 13, 2021. doi:10.14218/JCTH.2021.00065
    Abstract
    Liver fibrosis is a life-threatening disease, with challenging morbidity and mortality for healthcare systems worldwide. It imparts an enormous economic burden to societies, making [...] Read more.
    Liver fibrosis is a life-threatening disease, with challenging morbidity and mortality for healthcare systems worldwide. It imparts an enormous economic burden to societies, making continuous research and informational updates about its pathogenesis and treatment crucial. This review′s focus is on the current knowledge about the Wnt signaling pathway, serving as an important pathway in liver fibrosis development and activation of hepatic stellate cells (HSCs). Two types of Wnt pathways are distinguished, namely the ß-catenin-dependent canonical and non-canonical Ca2+ or planar cell polarity (PCP)-dependent pathway. The dynamic balance of physiologically healthy liver and hepatocytes is disturbed by repeated liver injuries. Activation of the ß-catenin Wnt pathway prevents the regeneration of hepatocytes by the replacement of extracellular matrix (ECM), leading to the appearance of scar tissue and the formation of regenerated nodular hepatocytes, lacking the original function of healthy hepatocytes. Therefore, liver function is reduced due to the severely advanced disease. Selective inhibition of ß-catenin inhibits inflammatory processes (since chemokines and pro-inflammatory cytokines are produced during Wnt activation), reduces growth of activated HSCs and reduces collagen synthesis and angiogenesis, thereby reducing the progression of liver fibrosis in vivo. While the canonical Wnt pathway is usually inactive in a physiologically healthy liver, it shows activity during cell regeneration or renewal and in certain pathophysiological conditions, such as liver diseases and cancer. Targeted blocking of some of the basic components of the Wnt pathway is a therapeutic approach. These include the frizzled transmembrane receptor (Fz) receptors using the secreted frizzled-related protein family (sFRP), Fz-coreceptors low-density LRP 5/6 through dickkopf-related protein 1 (DKK1) or niclosamide, glycogen kinase-3 beta (GSK-3β) using SB-216763, cyclic-AMP response element-binding protein (CBP) using PRI-724 and ICG-001, the lymphoid enhancer binding factor (LEF)/T cell-specific transcription factor (TCF) system as well as Wnt inhibitory factor 1 (WIF1) and miR-17-5p using pinostilbene hydrate (PSH). Significant progress has been made in inhibiting Wnt and thus stopping the progression of liver fibrosis by diminishing key components for its action. Comprehending the role of the Wnt signaling pathway in liver fibrosis may lead to discovery of novel targets in liver fibrosis therapeutic strategies’ development. Full article
    Original Article Open Access
    Prognostic Nomogram for Patients with Hepatitis E Virus-related Acute Liver Failure: A Multicenter Study in China
    Jian Wu, Cuifen Shi, Xinyu Sheng, Yanping Xu, Jinrong Zhang, Xinguo Zhao, Jiong Yu, Xinhui Shi, Gongqi Li, Hongcui Cao, Lanjuan Li
    Journal of Clinical and Translational Hepatology, Published online May 6, 2021. doi:10.14218/JCTH.2020.00117
    Abstract
    Timely and effective assessment scoring systems for predicting the mortality of patients with hepatitis E virus-related acute liver failure (HEV-ALF) are urgently needed. The present [...] Read more.
    Timely and effective assessment scoring systems for predicting the mortality of patients with hepatitis E virus-related acute liver failure (HEV-ALF) are urgently needed. The present study aimed to establish an effective nomogram for predicting the mortality of HEV-ALF patients. The nomogram was based on a cross-sectional set of 404 HEV-ALF patients who were identified and enrolled from a cohort of 650 patients with liver failure. To compare the performance with that of the model for end-stage liver disease (MELD) scoring and CLIF-Consortium-acute-on-chronic liver failure score (CLIF-C-ACLFs) models, we assessed the predictive accuracy of the nomogram using the concordance index (C-index), and its discriminative ability using time-dependent receiver operating characteristics (td-ROC) analysis, respectively. Multivariate logistic regression analysis of the development set carried out to predict mortality revealed that γ-glutamyl transpeptidase, albumin, total bilirubin, urea nitrogen, creatinine, international normalized ratio, and neutrophil-to-lymphocyte ratio were independent factors, all of which were incorporated into the new nomogram to predict the mortality of HEV-ALF patients. The area under the curve of this nomogram for mortality prediction was 0.671 (95% confidence interval: 0.602–0.740), which was higher than that of the MELD and CLIF-C-ACLFs models. Moreover, the td-ROC and decision curves analysis showed that both discriminative ability and threshold probabilities of the nomogram were superior to those of the MELD and CLIF-C-ACLFs models. A similar trend was observed in the validation set. The novel nomogram is an accurate and efficient mortality prediction method for HEV-ALF patients. Full article
    Original Article Open Access
    Underlying Causes of Death among Adults in the United States, 2013–2017
    Xin Hu, Yong Lin, Gangjian Qin, Lanjing Zhang
    Exploratory Research and Hypothesis in Medicine, Published online December 1, 2020. doi:10.14218/ERHM.2020.00065
    Abstract
    Overall mortality among U.S. adults has been stable in past years; however, racial disparity influenced 10 leading causes of death or age-specific mortality in Blacks or African Americans. [...] Read more.
    Overall mortality among U.S. adults has been stable in past years; however, racial disparity influenced 10 leading causes of death or age-specific mortality in Blacks or African Americans. Unfortunately, the trends in sex- and race-adjusted age-standardized cause-specific mortality are poorly understood. We here aimed to identify the underlying causes of death (UCD) with sex- and race-adjusted, and age-standardized mortality that has changed in recent years. We extracted the data of UCD from the Multiple Cause of Death database of the Centers for Disease Control and Prevention (CDC). Multivariable log-linear regression models were used to estimate trends in sex- and race-adjusted, and age-standardized mortality of UCD during 2013–2017. A total of 31,029,133 deaths were identified. Among the list of 113 UCDs compiled by the CDC, there were 29 UCDs exhibiting an upward trend, 33 UCDs exhibiting a downward trend and 56 UCDs with no significant trends. The 2 UCDs with the largest annual percent change were both nutrition related (annual percent change [APC] = 17.73, 95% CI [15.13–20.33] for malnutrition, and APC = 17.49, 95% CI [14.94–20.04] for Nutritional deficiencies), followed by accidental poisoning and exposure to noxious substances. The 4 UCDs with the largest decreasing APC were viral hepatitis (APC = −11.71), chronic and unspecified bronchitis (APC = −8.26), emphysema (APC = −7.11) and human immunodeficiency virus disease (APC = −7.10). This study thus reports UCDs with changing mortality in recent years after sex- and race-adjustments and age-standardizations. More effort and resources should focus on understanding, preventing and controling the mortality linked to these UCDs. Continuous monitoring of mortality trends is recommended. Full article
Special Features

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