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    Original Article Open Access
    Upregulation of GLT25D1 in Hepatic Stellate Cells Promotes Liver Fibrosis via the TGF-β1/SMAD3 Pathway In Vivo and In vitro
    Shiwei Wang, Lingling He, Fan Xiao, Meixin Gao, Herui Wei, Junru Yang, Yang Shu, Fuyang Zhang, Xiaohui Ye, Ping Li, Xiaohua Hao, Xingang Zhou, Hongshan Wei
    Journal of Clinical and Translational Hepatology, Published online May 26, 2022. doi:10.14218/JCTH.2022.00005
    Abstract
    Collagen β(1-O) galactosyltransferase 25 domain 1 (GLT25D1) is associated with collagen production and glycosylation, and its knockout in mice results in embryonic death. However, [...] Read more.
    Collagen β(1-O) galactosyltransferase 25 domain 1 (GLT25D1) is associated with collagen production and glycosylation, and its knockout in mice results in embryonic death. However, its role in liver fibrosis remains elusive, particularly in hepatic stellate cells (HSCs), the primary collagen-producing cells associated with liver fibrogenesis. Herein, we aimed to elucidate the role of GLT25D1 in HSCs. Bile duct ligation (BDL)-induced mouse liver fibrosis models, primary mouse HSCs (mHSCs), and transforming growth factor beta 1 (TGF-β1)-stimulated LX-2 human hepatic stellate cells were used in in vivo and in vitro studies. Stable LX-2 cell lines with either GLT25D1 overexpression or knockdown were established using lentiviral transfection. RNA-seq was performed to investigate the genomic differences. HPLC-MS/MS were used to identify glycosylation sites. Scanning electronic microscopy (SEM) and second-harmonic generation/two-photon excited fluorescence (SHG/TPEF) were used to image collagen fibril morphology. GLT25D1 expression was upregulated in nonparenchymal cells in human cirrhotic liver tissues. Meanwhile, its knockdown attenuated collagen deposition in BDL-induced mouse liver fibrosis and inhibited mHSC activation. GLT25D1 was overexpressed in activated versus quiescence LX-2 cells and regulated in vitro LX-2 cell activation, including proliferation, contraction, and migration. GLT25D1 also significantly increased liver fibrogenic gene and protein expression. GLT25D1 upregulation promoted HSC activation and enhanced collagen expression through the TGF-β1/SMAD signaling pathway. Mass spectrometry showed that GLT25D1 regulated the glycosylation of collagen in HSCs, affecting the diameter of collagen fibers. Collectively, the upregulation of GLT25D1 in HSCs promoted the progression of liver fibrosis by affecting HSCs activation and collagen stability. Full article
    Review Article Open Access
    Pregnancy and Metabolic-associated Fatty Liver Disease: A Clinical Update
    Sherouk Fouda, Madhu Mathew Vennikandam, Joseph M. Pappachan, Cornelius J. Fernandez
    Journal of Clinical and Translational Hepatology, Published online May 26, 2022. doi:10.14218/JCTH.2022.00052
    Abstract
    The intricate relationship between metabolic-associated fatty liver disease (MAFLD) and maternal complications has rapidly become a significant health threat in pregnant women. The [...] Read more.
    The intricate relationship between metabolic-associated fatty liver disease (MAFLD) and maternal complications has rapidly become a significant health threat in pregnant women. The presence of MAFLD in pregnancy increases the maternal risk of metabolic complications and comorbidities for both mother and baby. The preexistence or development of MAFLD in pregnancy is a complex multifactorial disorder that can lead to further complications for mother and baby. Therefore, as pregnant women are severely underrepresented in clinical research, there is a great need for a fair inclusion of this group in clinical trials. This review aims to explore the effects of MAFLD during pregnancy in the context of maternal complications and outcomes and explore the effects of pregnancy on the development and progression of MAFLD within the context of maternal obesity, altered metabolic profiles, gestational diabetes and altered hormonal profiles. We also addressed potential implications for the presence of MAFLD during pregnancy and its management in the clinical setting. Full article
    Case Report Open Access
    Paraneoplastic Anti-Tif1-gamma Autoantibody-positive Dermatomyositis as Clinical Presentation of Hepatocellular Carcinoma Recurrence
    Marco Ferronato, Claudine Lalanne, Chiara Quarneti, Michele Cevolani, Chiara Ricci, Alessandro Granito, Luigi Muratori, Marco Lenzi
    Journal of Clinical and Translational Hepatology, Published online May 24, 2022. doi:10.14218/JCTH.2021.00573
    Abstract
    Hepatocellular carcinoma (HCC) is rarely associated with autoimmune paraneoplastic syndromes. We report a case of anti-transcriptional intermediary factor-1 gamma (TIF1-γ)-positive [...] Read more.
    Hepatocellular carcinoma (HCC) is rarely associated with autoimmune paraneoplastic syndromes. We report a case of anti-transcriptional intermediary factor-1 gamma (TIF1-γ)-positive dermatomyositis (DM) as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue, myalgia, and typical skin rash. His medical history was notable for hepatitis C-related cirrhosis, successful treatment with direct-acting antiviral agents, and previously efficacious treatment of HCC. Laboratory testing showed significant rhabdomyolysis with anti-TIF1-γ antibodies at high titer, and DM was diagnosed. After a careful diagnostic workup, HCC recurrence was diagnosed. After first-line corticosteroid treatment, azathioprine and intravenous immunoglobulin treatments were administered; unfortunately, he mounted only partial response. Owing to the compromised performance status, no HCC treatment was feasible, and, according to international guidelines, he received only best supportive care. Here, we discuss the diagnostic, prognostic, and pathogenic roles of anti-TIF1-γ antibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients. Considering the TIF1 gene family’s established role in oncogenesis, we also review the role of TIF1-γ as a tumor-related neoantigen, leading to the development of clinically overt anti-TIF1-γ antibodies-positive DM. 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 ‘Novel Therapeutic Interventions for Neurodegenerative Disorders’

Journal: Journal of Exploratory Research in Pharmacology
Special Issue: Novel Therapeutic Interventions for Neurodegenerative Disorders
Submission deadline: November 30, 2022
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Integrative Omics Study for Clinical Liver Disease’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: Integrative Omics Study for Clinical Liver Disease
Submission deadline: October 31, 2022
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:
Abstract Submission:June 1, 2022
Manuscript Submission: December 31, 2022
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:
Abstract Submission:June 1, 2022
Manuscript Submission: December 31, 2022
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue 'Therapeutic strategies involving herbal medicines and bioactive ingredients for viral infections and secondary critical illness: interventions for inflammatory response and organ protection'

Journal: Future Integrative Medicine
Special Issue: Therapeutic strategies involving herbal medicines and bioactive ingredients for viral infections and secondary critical illness: interventions for inflammatory response and organ protection
Submission deadline:
Abstract Submission:June 1, 2022
Manuscript Submission: December 31, 2022
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
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Abstract Submission:June 1, 2022
Manuscript Submission: December 31, 2022
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Plant bioactives and their impact on psychological and cardiometabolic health’

Journal: Exploratory Research and Hypothesis in Medicine
Special Issue: Plant bioactives and their impact on psychological and cardiometabolic health
Submission deadline: October 31, 2022
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Call for Papers for Special Issue ‘Natural active ingredient–based nanodrug delivery system for cancer treatment’

Journal: Journal of Exploratory Research in Pharmacology
Special Issue: Natural active ingredient–based nanodrug delivery system for cancer treatment
Submission deadline: October 31, 2022
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Call for Papers for Special Issue ‘Artificial Intelligence in Liver Disease- Step towards Precision Medicine’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: Artificial Intelligence in Liver Disease- Step towords Precision Medicine
Submission deadline: July 31, 2022
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Acute liver failure (ALF)’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: Acute liver failure (ALF)
Submission deadline: August 31, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Metabolic dysfunction-associated fatty liver disease (MAFLD)’

Journal: Journal of Clinical and Translational Hepatology
Special Issue:Metabolic dysfunction-associated fatty liver disease (MAFLD)
Submission deadline: May 31, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Coronavirus Disease (COVID-19) and the Liver’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: Coronavirus Disease (COVID-19) and the Liver
Submission deadline: June 30, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Prevention & Control of Coronavirus Disease (COVID-19)

Journal: Exploratory Research and Hypothesis in Medicine
Special Issue: Prevention & Control of Coronavirus Disease (COVID-19)
Submission deadline: June 30, 2021
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Call for Papers for Special Issue ‘Treatment of Coronavirus Disease (COVID-19)’

Journal: Journal of Exploratory Research in Pharmacology
Special Issue: Treatment of Coronavirus Disease (COVID-19)
Submission deadline: June 30, 2021
Publication date: An article will be published online as soon as it is accepted