• Newly published articles
  • Highlights
    Original Article Open Access
    Network Pharmacology Elucidates the Anti-Inflammatory Mechanisms of QingFeiPaiDu Decoction for Treatment of COVID-19
    Yan Liu, Lewen Xiong, Yanyu Wang, Mengxiong Luo, Longfei Zhang, Yongqing Zhang
    Journal of Exploratory Research in Pharmacology , Published online July 30, 2021. doi:10.14218/JERP.2021.00011
    Abstract
    QingFeiPaiDu decoction (QFPDD) treatment benefits patients with coronavirus disease 2019 (COVID-19). This study aims to elucidate the mechanisms that underlie the anti-inflammatory [...] Read more.
    QingFeiPaiDu decoction (QFPDD) treatment benefits patients with coronavirus disease 2019 (COVID-19). This study aims to elucidate the mechanisms that underlie the anti-inflammatory effects of QFPDD. Based on the clinical symptoms of COVID-19 patients, a component-target-disease network was constructed using the network pharmacology method, and the potential active components, targets, and molecular mechanisms of QFPDD for the treatment of COVID-19 were screened using topology parameter analysis. The best molecules that were affected by QFPDD were validated using Real-Time quantitative polymerase chain reaction (RT-qPCR) in a cellular inflammation model. In total, 376 active ingredients were identified in QFPDD, and 18,833 potential anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets. The principal targets included PIK3CA, PIK3R1, APP, SRC, MAPK1, MAPK3, AKT1, HSP90AA1, EP300, and CDK1. Overall, 574 gene oncology entries and 214 signal pathways were identified. QFPDD affected the cellular response to nitrogen compounds, protein kinase activity, and membrane rafts. QFPDD modulated pathways that are associated with cancer, endocrine resistance, PI3K-Akt signaling, and proteoglycans in cancer. Molecular docking indicated that the core ingredients of QFPDD had a strong binding affinity for SARS-CoV-2 3-chymotrypsin-like cysteine protease (3CLpro) and angiotensin-converting enzyme 2 (ACE2). QFPDD treatment significantly mitigated the lipopolysaccharides-induced five targeted gene transcription in A549 cells. Our findings preliminarily elucidated that through its active ingredients QFPDD targeted 3CLpro and ACE2 to modulate many factors and pathways that are associated with the pathogenesis of COVID-19. The identified potential molecular mechanism, relevant factors, and key genes QFPDD targeted might help in the design of new and specific antiviral drugs. Full article
    Original Article Open Access
    Interaction of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 Increases Susceptibility to Nonalcoholic Steatohepatitis
    Ke Xu, Kenneth I. Zheng, Pei-Wu Zhu, Wen-Yue Liu, Hong-Lei Ma, Gang Li, Liang-Jie Tang, Rafael S. Rios, Giovanni Targher, Christopher D. Byrne, Xiao-Dong Wang, Yong-Ping Chen, Ming-Hua Zheng
    Journal of Clinical and Translational Hepatology, Published online July 29, 2021. doi:10.14218/JCTH.2021.00067
    Abstract
    Previous studies have reported that the single nucleotide polymorphisms (SNPs) of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic [...] Read more.
    Previous studies have reported that the single nucleotide polymorphisms (SNPs) of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease (NAFLD). However, no studies have examined the effect of interactions between these three genotypes to affect liver disease severity. We assessed the effect of these three SNPs on nonalcoholic steatohepatitis (NASH) and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD. We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD. Multivariable logistic regression analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409. Gene-gene interactions were analyzed by performing a generalized multifactor dimensionality reduction (GMDR) analysis. The mean ± standard deviation age of these 415 patients was 41.3±12.5 years, and 75.9% were men. Patients with SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH, even after adjustment for age, sex and body mass index. GMDR analysis showed that the combination of all three SNPs was the best model for predicting NASH. Additionally, the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C. NAFLD patients carrying the SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH. These three SNPs may synergistically interact to increase susceptibility to NASH. Full article
    Review Article Open Access
    Pharmacological Therapeutics: Current Trends for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)
    Thaninee Prasoppokakorn, Panyavee Pitisuttithum, Sombat Treeprasertsuk
    Journal of Clinical and Translational Hepatology, Published online July 28, 2021. doi:10.14218/JCTH.2021.00189
    Abstract
    Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term from nonalcoholic fatty liver disease (NAFLD) and is a positive diagnosis based on histopathology, imaging, [...] Read more.
    Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term from nonalcoholic fatty liver disease (NAFLD) and is a positive diagnosis based on histopathology, imaging, or blood biomarkers. MAFLD is one of the common causes of liver dysfunction worldwide, likely due to the increase in metabolic syndrome as well as the high burden of disease and its relationship to other extrahepatic conditions. However, effective pharmacological therapeutic agents are still lacking; current management largely focuses on weight reduction and lifestyle modification. The purpose of this review was to summarize the updated evidence of novel therapies targeting different pathogenetic pathways in MAFLD. Full article

Journals

  • Most viewed
  • Most cited
    Review Article Open Access
    Current Management of Alcoholic Hepatitis and Future Therapies
    Behnam Saberi, Alia S. Dadabhai, Yoon-Young Jang, Ahmet Gurakar, Esteban Mezey
    Journal of Clinical and Translational Hepatology, Published online June 28, 2016. doi:10.14218/JCTH.2016.00006
    Abstract
    Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. [...] Read more.
    Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. It encompasses a spectrum of disease, including fatty liver disease, alcoholic hepatitis (AH), and alcoholic cirrhosis. AH can range from mild to severe disease, with severe disease being defined as: Discriminant Function (DF) ≥ 32, or Model for End-stage Liver Disease (MELD) ≥ 21, or presence of hepatic encephalopathy. Management of the mild disease consists mainly of abstinence and supportive care. Severe AH is associated with significant mortality. Currently, there is no ideal medical treatment for this condition. Besides alcohol cessation, corticosteroids have been used with conflicting results and are associated with an inherent risk of infection. Overall steroids have shown short term benefit when compared to placebo, but they have no obvious long term benefits. Pentoxifylline does not improve survival in patients with severe AH and is no longer recommended based on the results of the STOPAH (Steroid Or Pentoxifylline for Alcoholic Hepatitis) trial. Anti-tumor necrosis factor (TNF) agents are associated with increased risk of life threatening infections and death. Currently, early stage trials are underway, mainly targeting novel pathways based on disease pathogenesis, including modulation of innate immune system, inhibition of gut-liver axis and cell death pathways, and activation of transcription factor farnesyl X receptor (FXR). Future treatment may lie in human induced pluripotent stem cell (iPSC) technology, which is currently under investigation for the study of pathogenesis, drug discovery, and stem cell transplantation. Liver transplantation has been reported with good results in highly selected patients but is controversial due to limited organ supply. Full article
    Review Article Open Access
    Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update
    Eric Yoon, Arooj Babar, Moaz Choudhary, Matthew Kutner, Nikolaos Pyrsopoulos
    Journal of Clinical and Translational Hepatology, Published online June 15, 2016. doi:10.14218/JCTH.2015.00052
    Abstract
    Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone [...] Read more.
    Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur. Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients. Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level, with focus on the underlying molecular signaling pathways. Full article
    Review Article Open Access
    Current Knowledge on Hepatitis E
    María Teresa Pérez-Gracia, Mario García, Beatriz Suay, María Luisa Mateos-Lindemann
    Journal of Clinical and Translational Hepatology, Published online June 15, 2015. doi:10.14218/JCTH.2015.00009
    Abstract
    Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates [...] Read more.
    Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin®. Full article
Special Features

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
Publication date: An article will be published online as soon as it is accepted

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