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    Review Article Open Access
    E-Cigarettes Promote Macrophage-Tumor Cells Crosstalk: Focus on Breast Carcinoma Progression and Lung Metastasis
    Kien Pham, Sam DeFina, He Wang
    Exploratory Research and Hypothesis in Medicine, Published online February 24, 2021. doi:10.14218/ERHM.2021.00002
    Abstract
    Recurrence and metastasis are the foremost causes of morbidity and mortality for breast cancer (BC). Recent studies have highlighted the critical role of the tumor microenvironment, [...] Read more.
    Recurrence and metastasis are the foremost causes of morbidity and mortality for breast cancer (BC). Recent studies have highlighted the critical role of the tumor microenvironment, in particular, because it is related to tumor-associated macrophages (TAMs), in metastasis of BC. TAMs are mainly derived from macrophages that are recruited by C-C motif chemokine ligand 5, which are secreted by cancer cells and cancer-related stromal cells. Although E-cigarettes (E-cigs) were originally proposed as a healthy substitute for conventional cigarette smoking, clinical and experimental evidence has highlighted the potentially lethal effects of this alternative. Several studies have illustrated the immune or macrophage activation and DNA damaging effects of E-cigs. However, the potentially pivotal role of TAM-BC crosstalk during BC progression and metastasis for E-cig vaping has not been explored. This review discussed the significant effect that E-cig use had on the BC tumor microenvironment, which ultimately led to enhanced tumor malignancy and metastasis, with an emphasis on the extent that E-cig uses had on the crosstalk between cancer and immune cells, as well as the potential underlying mechanisms that drive this aggressive phenotype of BC. This review advances our understanding of this matter and provides scientific evidence that could highlight risks associated with vaping and suggest a potential intervention for the treatment of aggressive BCs that present an increased risk of metastasis. Full article
    Hypothesis Open Access
    Potential Role of Galectin-glycan Lattices in SARS-CoV-2 Infection and Pathogenesis: A Hypothesis
    Enrique Arciniegas, Luz Marina Carrillo, Antonio Salgado
    Exploratory Research and Hypothesis in Medicine, Published online February 22, 2021. doi:10.14218/ERHM.2020.00079
    Abstract
    Endothelial dysfunction plays a crucial role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and has recently been proposed to be connected with acute thrombosis, [...] Read more.
    Endothelial dysfunction plays a crucial role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and has recently been proposed to be connected with acute thrombosis, hyper-inflammation, cytokine storm syndrome, immune cell recruitment, platelet aggregation, vasoconstriction and endothelial apoptosis. Importantly, certain mediators and pro-inflammatory cytokines such as galectin (Gal) 1, Gal3 and Gal8 act in a concerted manner through the N- and O-linked glycans located on the SARS-CoV-2 S protein. We hypothesize that the presence of these factors may cause the ACE2 receptor, integrin β1, and CD44 to generate a Gal-glycan lattice on the surface of SARS-CoV-2 virus. This lattice, in addition to endothelial cells (ECs), may not only influence EC behavior and the inflammatory response, but may also induce conformational changes in the viral structure that can facilitate attachment and entry into the ECs. We believe that further basic science research is necessary to elucidate the composition and role of the Gal-glycan lattices in the SARS-CoV-2 infection. Full article
    Original Article Open Access
    Associations of Hydroxysteroid 17-beta Dehydrogenase 13 Variants with Liver Histology in Chinese Patients with Metabolic-associated Fatty Liver Disease
    Wen-Yue Liu, Mohammed Eslam, Kenneth I. Zheng, Hong-Lei Ma, Rafael S. Rios, Min-Zhi Lv, Gang Li, Liang-Jie Tang, Pei-Wu Zhu, Xiao-Dong Wang, Christopher D. Byrne, Giovanni Targher, Jacob George, Ming-Hua Zheng
    Journal of Clinical and Translational Hepatology, Published online February 22, 2021. doi:10.14218/JCTH.2020.00151
    Abstract
    In Europeans, variants in the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene impact liver histology in metabolic-associated fatty liver disease (MAFLD). The [...] Read more.
    In Europeans, variants in the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene impact liver histology in metabolic-associated fatty liver disease (MAFLD). The impact of these variants in ethnic Chinese is unknown. The aim of this study was to investigate the potential associations in Chinese patients. In total, 427 Han Chinese with biopsy-confirmed MAFLD were enrolled. Two single nucleotide polymorphisms in HSD17B13 were genotyped: rs72613567 and rs6531975. Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology. In our cohort, the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis [odds ratio (OR): 2.93 (1.20–7.17), p=0.019 for the additive model; OR: 3.32 (1.39–7.91), p=0.007 for the recessive model], representing an inverse association as compared to the results from European cohorts. In contrast, we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant [OR: 0.48 (0.24–0.98), p=0.043 for the additive model; OR: 0.62 (0.40–0.94), p=0.025 for the dominant model]. HSD17B13 variants were only associated with fibrosis but no other histological features. Furthermore, HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis. HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans. These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals. Full article

Journals

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    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 ‘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