Wilson disease (WD) is a potentially treatable, inherited disorder of copper metabolism characterised by pathological copper accumulation. WD is caused by mutations in the ATP7B gene, which encodes a transmembrane copper-transporting ATPase, leading to copper overload in the liver, brain and other organs. The clinical course of WD can vary in severity but progressive liver disease is a common feature. Patients can also present with neurological disorders and psychiatric symptoms. WD is diagnosed based on diagnostic algorithms incorporating clinical symptoms and signs, measures of copper metabolism and DNA analysis. Available treatments include chelators and zinc salts, which reverse copper overload by different mechanisms. Additionally, liver transplantation is indicated in selected cases. New agents, such as tetrathiomolybdate salts, are currently being investigated in clinical trials and genetic therapies are being tested in animal models. With early treatment, the prognosis of disease is good; however, an important issue is diagnosing patients before the onset of serious symptoms. Advances in screening for WD may therefore bring earlier diagnosis and improvements for patients with this disorder.

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Nature Reviews Disease Primers article: Wilson disease

Background:Clinical presentations of Wilson's disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, whereas neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24-hour urinary copper ex

Wilson's Disease in Children : A Position Paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition

Liver biopsy is required when clinically important information about the diagnosis, prognosis or management of a patient cannot be obtained by safer means, or for research purposes. There are several approaches to liver biopsy but predominantly percutaneous or transvenous approaches are used. A wide choice of needles is available and the approach and type of needle used will depend on the clinical state of the patient and local expertise but, for non-lesional biopsies, a 16-gauge needle is recommended. Many patients with liver disease will have abnormal laboratory coagulation tests or receive anticoagulation or antiplatelet medication. A greater understanding of the changes in haemostasis in liver disease allows for a more rational, evidence-based approach to peri-biopsy management. Overall, liver biopsy is safe but there is a small morbidity and a very small mortality so patients must be fully counselled. The specimen must be of sufficient size for histopathological interpretation. Communication with the histopathologist, with access to relevant clinical information and the results of other investigations, is essential for the generation of a clinically useful report.

https://gut.bmj.com/content/gutjnl/69/8/1382.full.pdf

Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology

[guillain-barr'e syndrome].

Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along with their resistant strains, new pathogenic viruses continue to be discovered so creating an ongoing need for new antiviral treatments. RNA interference is a cellular gene-silencing phenomenon in which sequence-specific degradation of target mRNA is achieved by means of complementary short interfering RNA (siRNA) molecules. Short interfering RNA technology affords a potential tractable strategy to combat viral pathogenesis because siRNAs are specific, easy to design, and can be directed against multiple strains of a virus by targeting their conserved gene regions. In this review, we briefly summarize the current status of siRNA therapy for representative examples from different virus families. In addition, other aspects like their design, delivery, medical significance, bioinformatics resources, and limitations are also discussed.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/rmv.1976

A review on current status of antiviral siRNA.

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.27932

Prospective evaluation of the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample

The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis is an iron-mediated form of cell death caused by the accumulation of lipid peroxides. The intracellular imbalance between oxidant and antioxidant due to the abnormal expression of multiple redox active enzymes will promote the produce of reactive oxygen species (ROS). So far, a few pathways and regulators have been discovered to regulate ferroptosis. In particular, the cystine/glutamate antiporter (System Xc −), glutathione peroxidase 4 (GPX4) and glutathione (GSH) (System Xc −/GSH/GPX4 axis) plays a key role in preventing lipid peroxidation-mediated ferroptosis, because of which could be inhibited by blocking System Xc −/GSH/GPX4 axis. This review aims to present the current understanding of the mechanism of ferroptosis based on the System Xc −/GSH/GPX4 axis in the treatment of drug-resistant solid tumors.

System Xc −/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy

Alzheimer’s disease (AD), the most common type of senile dementia, includes the complex pathogenesis of abnormal deposition of amyloid beta-protein (Aβ), phosphorylated tau (p-tau) and neuroimmune inflammatory. The neurodegenerative process of AD triggers microglial activation, and the overactivation of microglia produces a large number of neuroimmune inflammatory factors. Microglia dysfunction can lead to disturbances in iron metabolism and enhance iron-induced neuronal degeneration in AD, while elevated iron levels in brain areas affect microglia phenotype and function. In this manuscript, we firstly discuss the role of microglia in AD and then introduce the role of microglia in the immune-inflammatory pathology of AD. Their role in AD iron homeostasis is emphasized. Recent studies on microglia and ferroptosis in AD are also reviewed. It will help readers better understand the role of microglia in iron metabolism in AD, and provides a basis for better regulation of iron metabolism disorders in AD and the discovery of new potential therapeutic targets for AD.

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The Role of Microglia in Alzheimer’s Disease From the Perspective of Immune Inflammation and Iron Metabolism

Guillain-Barre syndrome (GBS) is a rare neurological complication of hepatitis B. GBS presence in acute hepatitis E virus (HEV) and cytomegalovirus (CMV) infection is also sporadically reported. Here, a rare case of GBS in a chronic Hepatitis B virus carrier co-infected with HEV and CMV was reported. Based on the analysis on the progress of the manifestations and virus serological detection results, it could be concluded that GBS might mostly likely result from super-infection of HEV and CMV. This case report is clinically important in that it provides a good example of differential diagnosis and appropriate treatment on such a rare but life-threatening case. J. Med. Virol. 89:368-372, 2017. © 2016 Wiley Periodicals, Inc.

Guillain-Barré syndrome following acute co-super-infection of hepatitis E virus and cytomegalovirus in a chronic hepatitis B virus carrier.

Malignant tumor is a major killer that seriously endangers human health. At present, the methods of treating tumors include surgical resection, chemotherapy, radiotherapy and immunotherapy. However, the survival rate of patients is still very low due to the complicated mechanism of tumor occurrence and development and high recurrence rate. Individualized treatment will be the main direction of tumor treatment in the future. Because only by understanding the molecular mechanism of tumor development and differentially expressed genes can we carry out accurate treatment and improve the therapeutic effect. MicroRNA (miRNA) is a kind of small non coding RNA, which regulates gene expression at mRNA level and plays a key role in tumor regulation. Ferroptosis is a kind of programmed death caused by iron dependent lipid peroxidation, which is different from apoptosis, necrosis and other cell death modes. Now it has been found that ferroptosis plays an important role in the occurrence and development of tumors and drug resistance. More and more studies have found that miRNAs can regulate tumor development and drug resistance through ferroptosis. Therefore, in this review, the mechanism of ferroptosis is briefly outlined, and the relationship between miRNAs and ferroptosis in tumors is reviewed.

https://www.frontiersin.org/articles/10.3389/fphar.2022.977062/pdf

Hong-yu Luo

Papers

Prospective evaluation of the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample

System Xc −/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy

The Role of Microglia in Alzheimer’s Disease From the Perspective of Immune Inflammation and Iron Metabolism

Guillain-Barré syndrome following acute co-super-infection of hepatitis E virus and cytomegalovirus in a chronic hepatitis B virus carrier.

Relationship between miRNA and ferroptosis in tumors