No abstract

Bacterial translocation (BT) has been impeccably implicated as a driving factor in the pathogenesis of a spectrum of chronic liver diseases (CLD). Scientific evidence accumulated over the last four decades has implied that the disease pathologies in CLD and BT are connected as a loop in the gut-liver axis and exacerbate each other. Pregnane X receptor (PXR) is a ligand-activated transcription factor and nuclear receptor that is expressed ubiquitously along the gut-liver-axis. PXR has been intricately associated with the regulation of various mechanisms attributed in causing BT. The importance of PXR as the mechanistic linker molecule in the gut-liver axis and its role in regulating bacterial interactions with the host in CLD has not been explored. PubMed was used to perform an extensive literature search using the keywords PXR and bacterial translocation, PXR and chronic liver disease including cirrhosis. In an adequate expression state, PXR acts as a sensor for bile acid dysregulation and bacterial derived metabolites, and in response shapes the immune profile beneficial to the host. Activation of PXR could be therapeutic in CLD as it counter-regulates endotoxin mediated inflammation and maintains the integrity of intestinal epithelium. This review mainly focuses PXR function and its regulation in BT in the context of chronic liver diseases.

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Patients affected by coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, manifest various gastrointestinal and hepatic abnormalities alongside respiratory disorders. The identification of this virus in the feces of more than 50% of infected individuals indicates the possibility of viral shedding and fecal-to-oral transmission. Preliminary reports have also identified alterations in the intestinal microbiota profile in infected individuals. Moreover, COVID-19 patients manifest various degrees of liver injury characterized by alterations in liver enzymes. Digestive symptoms and liver abnormalities correlate with disease severity, the incidence of critical outcomes and patient's recovery. However, the pathogenic mechanisms behind COVID-19-induced abnormalities in the gut-liver axis seem to be multifactorial in origin. This review compiles current knowledge sourced from preclinical and clinical research and summarizes gastrointestinal and hepatic dysfunctions observed following SARS-CoV-2 infection, and also explores the possible mechanisms generating abnormalities in the gut-liver axis. Furthermore, this review sheds light on possible therapeutic targets against these disorders.

With the ongoing pandemic of coronavirus disease 2019 (COVID-19), many neurological manifestations have been linked to what began as an outbreak of atypical pneumonia. Like other corona viruses, severe acute respiratory syndrome coronavirus (SARS-CoV-2) has potential for neurotropism. Viral invasion and likely pathogenecity has been associated with expression of ACE-2 receptors along endothelia and olfactory mucosa. Hyperinflammatory response after systemic infection is in part responsible for the severity and multi-organ dysfunction seen in severe cases. Features like encephalitis, central and peripheral demyelinating disorders, cranial neuropathies, stroke are seen not only in patients with severe illness but at times preceding any systemic symptoms. Neurological disorders are not only part of acute illness phase but also seen in postinfectious phase likely due to immune mediated effect. Also, long term sequelae in patients with moderate to severe COVID-19, either due to systemic complications or direct virus mediated effect are a matter of concern. High suspicion and early recognition of possible presenting features and neurological complications in severely affected patients is key for management. With the rapidity and enormity of ongoing pandemic whether these observations are causal or casual is yet to be determined. Further collaborations for comparisons of observations across the world in necessary to understand the potential impact of COVID-19. Accessing these observations will help in better understanding the agent host and environmental factors determining the expected impact of this pandemic. Reorganizing health care facilities to apt for better handling COVID-19 over time to come will help to mitigate the impact. Keywords: COVID-19; neurological manifestations; encephalitis; stroke; neurotropism