Alterations in Expression and Function of ABC Family Transporters at Blood-Brain Barrier under Liver Failure and Their Clinical Significances

Fan, Yilin; Liu, Xiaodong

doi:10.3390/pharmaceutics10030102

Cited by 16 publications

(7 citation statements)

References 95 publications

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“…Moreover, hyperammonemia increases the expression of P-glycoprotein and Mrp2 by activating the NF-kB pathway in the BBB ( Zhang et al, 2014 ). In ALF, the expression and function of ABC transporters in the BBB are also altered ( Fan and Liu, 2018 ).…”

Section: Blood–brain Barrier Permeabilitymentioning

confidence: 99%

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

Chen

Ruan

et al. 2021

Front. Cell. Infect. Microbiol.

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Hepatic encephalopathy (HE) is a neurological disorder that occurs in patients with liver insufficiency. However, its pathogenesis has not been fully elucidated. Pharmacotherapy is the main therapeutic option for HE. It targets the pathogenesis of HE by reducing ammonia levels, improving neurotransmitter signal transduction, and modulating intestinal microbiota. Compared to healthy individuals, the intestinal microbiota of patients with liver disease is significantly different and is associated with the occurrence of HE. Moreover, intestinal microbiota is closely associated with multiple links in the pathogenesis of HE, including the theory of ammonia intoxication, bile acid circulation, GABA-ergic tone hypothesis, and neuroinflammation, which contribute to cognitive and motor disorders in patients. Restoring the homeostasis of intestinal bacteria or providing specific probiotics has significant effects on neurological disorders in HE. Therefore, this review aims at elucidating the potential microbial mechanisms and metabolic effects in the progression of HE through the gut–brain axis and its potential role as a therapeutic target in HE.

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Section: Blood–brain Barrier Permeabilitymentioning

confidence: 99%

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

Chen

Ruan

et al. 2021

Front. Cell. Infect. Microbiol.

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“…However, which components of HE lead to increased susceptibility is not clear. BBB alterations (increased permeability) in patients suffering from HE may lead to vulnerability [50], particularly in regards to immunosuppression neurotoxicity during the early days following LT [51]. In acute liver failure (ALF), intracranial hypertension impairs cerebral blood flow [52] increasing the risk of brain injury during LT [53].…”

Section: He: the Vulnerable Brainmentioning

confidence: 99%

Hepatic Encephalopathy: From Metabolic to Neurodegenerative

2021

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Hepatic encephalopathy (HE) is a neuropsychiatric syndrome of both acute and chronic liver disease. As a metabolic disorder, HE is considered to be reversible and therefore is expected to resolve following the replacement of the diseased liver with a healthy liver. However, persisting neurological complications are observed in up to 47% of transplanted patients. Several retrospective studies have shown that patients with a history of HE, particularly overt-HE, had persistent neurological complications even after liver transplantation (LT). These enduring neurological conditions significantly affect patient's quality of life and continue to add to the economic burden of chronic liver disease on health care systems. This review discusses the journey of the brain through the progression of liver disease, entering the invasive surgical procedure of LT and the conditions associated with the post-transplant period. In particular, it will discuss the vulnerability of the HE brain to peri-operative factors and post-LT conditions which may explain non-resolved neurological impairment following LT. In addition, the review will provide evidence; (i) supporting overt-HE impacts on neurological complications post-LT; (ii) that overt-HE leads to permanent neuronal injury and (iii) the pathophysiological role of ammonia toxicity on astrocyte and neuronal injury/damage. Together, these findings will provide new insights on the underlying mechanisms leading to neurological complications post-LT.

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“…However, as normal tissue stem cells are also maintained by the upregulated expression of ABC transporters, inhibition of the transporter family will be harmful for those cells. Furthermore, brain microvessel endothelial cells, which constitute blood brain barriers, are known to be maintained by ABC transporters including ABCG2 and ABCB1 [ 85 ] . Therefore, eliminating CSCs by the inhibition of ABC transporters might be a double-edged sword.…”

Section: Mechanisms Of Cscs’ Therapy Resistance and Their Potential A...mentioning

confidence: 99%

Drug resistance mechanisms of cancer stem-like cells and their therapeutic potential as drug targets

Murayama¹,

Gotoh²

2019

CDR

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Despite of recent advances in cancer research and development of new anti-cancer drugs, tumor patients' prognoses have not yet been improved well enough. Treatment failure of tumors is highly attributed to the drug resistance of a small population of cancer cell known as cancer stem-like cells (CSCs). CSCs also have the self-renewal activity and differentiation potency, conferring strong tumorigenicity on them. Therefore, development of CSC targeting therapy is urgently needed in order to overcome possible recurrence and metastasis by them after therapy. CSCs show some characteristic features that are not observed in other differentiated cancer cells, which give them higher resistance against conventional chemotherapy or radiotherapy. Targeting such specific features could be useful for CSC eradication. This review will summarize the recent advances in the study of CSC characteristics along with the promising therapeutic strategies targeting them.

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Alterations in Expression and Function of ABC Family Transporters at Blood-Brain Barrier under Liver Failure and Their Clinical Significances

Cited by 16 publications

References 95 publications

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

Hepatic Encephalopathy: From Metabolic to Neurodegenerative

Drug resistance mechanisms of cancer stem-like cells and their therapeutic potential as drug targets

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