scholarly journals Hepatic IFNL4 Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology

2021 ◽  
Vol 22 (15) ◽  
pp. 7803
Author(s):  
Henriette Huschka ◽  
Sabine Mihm

Hepatocellular carcinoma (HCC) is a malignancy with a leading lethality. The etiology is quite diverse, ranging from viral infections to metabolic disorders or intoxications, and associates with specific somatic mutational patterns and specific host immunological phenotypes. Particularly, hepatitis C virus (HCV)-infected liver is featured by an activation of interferon (IFN)-stimulated genes (ISGs; IFN signature), which we suppose is driven by type III IFNL4. Taking advantage of the TCGA collection of HCC patients of various different etiologies, this study aimed at validating our previous findings on hepatic IFNL4 gene activation in HCV infection in an independent and larger cohort of patients with advanced liver disease. In a cohort of n = 377 cases, the entirety of the sequencing data was used to assess the IFNL genotypes, and the cases were stratified for etiology. The number of IFNL4 transcripts within nonmalignant and malignant tissues was found to be more abundant in patients with HCV or HCV/HBV infections when compared to other risk factors. Moreover, in patients with HCV infection as a risk factor, a close, positive relationship was found between ISG activation and the number of functional IFNL4 transcripts. Data on this independent TCGA sample support the concept of an IFNL4-dependent HCV-driven activation of hepatic ISGs. In addition to that, they add to the understanding of etiology-related host immunological phenotypes in HCC.

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Preston Leung ◽  
Rowena Bull ◽  
Andrew Lloyd ◽  
Fabio Luciani

Rapidly mutating viruses, such as hepatitis C virus (HCV) and HIV, have adopted evolutionary strategies that allow escape from the host immune response via genomic mutations. Recent advances in high-throughput sequencing are reshaping the field of immuno-virology of viral infections, as these allow fast and cheap generation of genomic data. However, due to the large volumes of data generated, a thorough understanding of the biological and immunological significance of such information is often difficult. This paper proposes a pipeline that allows visualization and statistical analysis of viral mutations that are associated with immune escape. Taking next generation sequencing data from longitudinal analysis of HCV viral genomes during a single HCV infection, along with antigen specific T-cell responses detected from the same subject, we demonstrate the applicability of these tools in the context of primary HCV infection. We provide a statistical and visual explanation of the relationship between cooccurring mutations on the viral genome and the parallel adaptive immune response against HCV.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1681
Author(s):  
José Debes ◽  
Pablo Romagnoli ◽  
Jhon Prieto ◽  
Marco Arrese ◽  
Angelo Mattos ◽  
...  

Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Major etiologies of HCC relate to chronic viral infections as well as metabolic conditions. The survival rate of people with HCC is very low and has been attributed to late diagnosis with limited treatment options. Combining ultrasound and the biomarker alpha-fetoprotein (AFP) is currently one of the most widely used screening combinations for HCC. However, the clinical utility of AFP is controversial, and the frequency and operator-dependence of ultrasound lead to a variable degree of sensitivity and specificity across the globe. In this review, we summarize recent developments in the search for non-invasive serum biomarkers for early detection of HCC to improve prognosis and outcome for patients. We focus on tumor-associated protein markers, immune mediators (cytokines and chemokines), and micro-RNAs in serum or circulating extracellular vesicles and examine their potential for clinical application.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Niina Haiminen ◽  
Filippo Utro ◽  
Ed Seabolt ◽  
Laxmi Parida

AbstractIn response to the ongoing global pandemic, characterizing the molecular-level host interactions of the new coronavirus SARS-CoV-2 responsible for COVID-19 has been at the center of unprecedented scientific focus. However, when the virus enters the body it also interacts with the micro-organisms already inhabiting the host. Understanding the virus-host-microbiome interactions can yield additional insights into the biological processes perturbed by viral invasion. Alterations in the gut microbiome species and metabolites have been noted during respiratory viral infections, possibly impacting the lungs via gut-lung microbiome crosstalk. To better characterize microbial functions in the lower respiratory tract during COVID-19 infection, we carry out a functional analysis of previously published metatranscriptome sequencing data of bronchoalveolar lavage fluid from eight COVID-19 cases, twenty-five community-acquired pneumonia patients, and twenty healthy controls. The functional profiles resulting from comparing the sequences against annotated microbial protein domains clearly separate the cohorts. By examining the associated metabolic pathways, distinguishing functional signatures in COVID-19 respiratory tract microbiomes are identified, including decreased potential for lipid metabolism and glycan biosynthesis and metabolism pathways, and increased potential for carbohydrate metabolism pathways. The results include overlap between previous studies on COVID-19 microbiomes, including decrease in the glycosaminoglycan degradation pathway and increase in carbohydrate metabolism. The results also suggest novel connections to consider, possibly specific to the lower respiratory tract microbiome, calling for further research on microbial functions and host-microbiome interactions during SARS-CoV-2 infection.


2016 ◽  
Vol 64 (2) ◽  
pp. S333-S334
Author(s):  
F. Morisco ◽  
M. Guarino ◽  
R. Valvano ◽  
N. Caporaso ◽  
F. Farinati ◽  
...  

RSC Advances ◽  
2015 ◽  
Vol 5 (99) ◽  
pp. 80956-80966 ◽  
Author(s):  
Vaishaali Natarajan ◽  
Eric J. Berglund ◽  
Dorothy X. Chen ◽  
Srivatsan Kidambi

Liver fibrosis occurs as a consequence of chronic injuries from viral infections, metabolic disorders, and alcohol abuse.


Author(s):  
Simran Kaur ◽  
Nikita Sharma ◽  
Arpita Roy

Background: The plant, Cannabis sativa is heavily explored and researched with many industrial and pharmaceutical applications. The medicinal and therapeutic role of cannabis Sativa has been summarized in the paper, citing its mechanism of action and influence on the human body. Diseases like metabolic disorders, infectious diseases, and psychological disorders pose negative and long-term drastic effects on the body like neurodegeneration and other chronic system failures. Several existing literature has proved its effectiveness against such diseases. Objectives: This review aims to provide an overview of the role of cannabinoids in various diseases like metabolic disorders, infectious diseases, and psychological disorders. Method: Various e-resources like Pubmed, Science Direct, and Google Scholar were thoroughly searched and read to form a well-informed and information-heavy manuscript. Here we tried to summaries the therapeutic aspect of Cannabis sativa and its bioactive compound cannabinoids in various diseases. Result: This review highlights the various constituents which are present in Cannabis sativa, the Endocannabinoid system, and the role of cannabinoids in various diseases Conclusion: Recent research on Cannabis has suggested its role in neurodegenerative diseases, inflammation, sleep disorders, pediatric diseases, and their analgesic nature. Therefore, the authors majorly focus on the therapeutic aspect of Cannabis sativa in various diseases. The focus is also on the endocannabinoid system (ECS) and its role in fighting or preventing bacterial, parasitic, fungal, and viral infections.


2006 ◽  
Vol 290 (5) ◽  
pp. G847-G851 ◽  
Author(s):  
Jinah Choi ◽  
J.-H. James Ou

Hepatitis C virus (HCV) is a major cause of viral hepatitis that can progress to hepatic fibrosis, steatosis, hepatocellular carcinoma, and liver failure. HCV infection is characterized by a systemic oxidative stress that is most likely caused by a combination of chronic inflammation, iron overload, liver damage, and proteins encoded by HCV. The increased generation of reactive oxygen and nitrogen species, together with the decreased antioxidant defense, promotes the development and progression of hepatic and extrahepatic complications of HCV infection. This review discusses the possible mechanisms of HCV-induced oxidative stress and its role in HCV pathogenesis.


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