Bilirubin, the primary breakdown product of hemoproteins, particularly hemoglobin, plays a key role in the diagnosis, prognosis, and monitoring of liver diseases. In acute liver diseases, such as acute liver failure, drug-induced liver injury, and viral hepatitis, bilirubin serves as a biomarker reflecting the extent of hepatocyte loss and liver damage. Chronic liver diseases, including alcohol-related liver disease, chronic hepatitis C virus infection, metabolic dysfunction-associated fatty liver disease, and autoimmune liver diseases, are marked by persistent liver injury and inflammation. Bilirubin levels in chronic liver diseases provide insight into liver function, disease severity, and prognosis. As a versatile biomarker, bilirubin offers valuable information on the pathophysiology of liver diseases and aids in guiding clinical decision-making regarding the treatment of liver diseases and their complications. This review aimed to explore the multifunctional role of bilirubin in liver diseases by analyzing its biological functions beyond its role as a biomarker of liver damage.

Acetaminophen (APAP)-induced liver injury (AILI) has an increasing incidence worldwide. However, the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently available. The study aimed to investigate the effect of BTF3L4 overexpression on apoptosis and inflammation regulation in vitro and in vivo.

We performed a proteomic analysis of the AILI model and found basic transcription factor 3 like 4 (BTF3L4) was the only outlier transcription factor overexpressed in the AILI model in mice. BTF3L4 overexpression increased the degree of liver injury in the AILI model.

BTF3L4 exerts its pathogenic effect by inducing an inflammatory response and damaging mitochondrial function. Increased BTF3L4 expression increases the degree of apoptosis, reactive oxygen species generation, and oxidative stress, which induces cell death and liver injury. The damage of mitochondrial function by BTF3L4 triggers a cascade of events, including reactive oxygen species accumulation and oxidative stress. According to the available AILI data, BTF3L4 expression is positively associated with inflammation and may be a potential biomarker of AILI.

Our results suggest that BTF3L4 is a pathogenic factor in AILI and may be a potential diagnostic maker for AILI.

Chronic hepatitis B remains the primary cause of liver-related events in China. The World Health Organization set a goal to eliminate viral hepatitis as a public health threat by 2030. However, achieving this goal appears challenging due to the current low rates of diagnosis and treatment. The “Treat-all” strategy, which proposes treating all patients with detectable hepatitis B virus (HBV) DNA or even all patients with positive HBsAg, has been suggested to simplify anti-HBV treatment. In 2022, the Chinese Society of Hepatology and the Chinese Society of Infectious Diseases updated the guidelines for the prevention and treatment of chronic hepatitis B in China, expanding antiviral indications and simplifying the treatment algorithm. According to this latest guideline, nearly 95% of patients with detectable HBV DNA are eligible for antiviral treatment. This review aimed to provide a detailed interpretation of the treatment indications outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022) and to identify gaps in achieving the “Treat-all” strategy in China.

Cholestatic liver disease is a group of diseases in which bile acid accumulates in the liver for various reasons, resulting in abnormal liver biochemical indicators and histological damage. Cholestasis can be divided into intrahepatic cholestasis and extrahepatic cholestasis, which will contribute to liver damage and progress to liver fibrosis and cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis are the two most typical cholestatic liver diseases. Ursodeoxycholic acid is currently the first-line treatment for PBC, while obeticholic acid, budesonide and fibrates have also shown good potential in the treatment of PBC. There are currently no official drugs approved to treat primary sclerosing cholangitis, and the use of ursodeoxycholic acid may have certain clinical benefits. At present, progress has been made in new treatment directions for cholestatic liver disease, including fibroblast growth factor 19, cholestyramine, S-adenosyl-L-methionine, steroid drugs, farnesoid X receptor agonists, and more. Considerable progress has been made in the management of cholestatic liver disease but there are still many opportunities and challenges. In this review, we summarized the recommended guidelines for the management of cholestatic disease and the progress of new drug research and development, in order to provide an important reference for the clinical practice of cholestatic liver disease.

Olaparib is a selective poly (ADP-ribose) polymerase inhibitor. However, its clinical application is hindered by low solubility and undesired pharmacokinetic profiles (e.g., relatively short circulation). Therefore, the present study aims to exploit polymeric micelles as a safe solubilizer and nanocarrier of olaparib, in order to improve its solubility and pharmacokinetics.

Poly (ε-caprolactone)-co-poly (benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate), i.e., benzyl-functionalized trimethylene carbonate)-b-poly (ethylene glycol) (P(CL-co-TMC-Bz)-PEG), was synthesized by ring-opening polymerization, and used to prepare the π-π-stacked polymeric micelles for olaparib encapsulation. A series of olaparib-loaded micelles with different polymer concentrations and wt% loadings were prepared using different methods to investigate the effect of formulation variables on the size of polymeric micelles and drug loadings. In addition, the in vitro release of olaparib from the micelles, and the cytotoxicity of micellar olaparib formulations on the SKOV3 tumor cell line were evaluated by UV spectrophotometry and CCK-8 assay, respectively. Finally, the blood circulation kinetics and side effects of the incorporated olaparib in the micelles and free olaparib were investigated in SD rats using ultra-high performance liquid chromatography analysis and H&E staining, respectively.

It was found that P(CL11-co-TMC-Bz5)-PEG micelles served as a safe and excellent solubilizer for olaparib, and that the solubilization capacity was easily tailored by adjusting the polymer concentration. In addition, when loaded in micelles, olaparib exhibited a sustained release behavior in vitro, and obvious cytotoxicity on SKOV3 cells. The in vivo studies revealed that olaparib incorporated in P(CL11-co-TMC-Bz5)-PEG polymeric micelles exhibited prolonged circulation (t1/2 = 2.00 hours), when compared to free olaparib (t1/2 ≤ 0.25 hours), and excellent safety. However, in terms of taking advantage of the EPR effect of the micelle delivery system to achieve the targeted olaparib delivery, the circulation time of olaparib in the micelles remained rather short.

Improvements, such as chemical crosslinking and drug conjugation, are required to improve the retention of olaparib-loaded polymeric micelles in blood circulation, and benefit from the use of micelles as a targeted delivery system.

The most prevalent form of dementia, Alzheimer’s disease (AD), is a neurological disorder that causes gradual memory loss. AD is characterized by amyloid-beta plaques, neurofibrillary tangles, and neuron loss. While preclinical and clinical trials are underway to reduce the generation and overall brain disease load, current treatment focuses on alleviating symptoms. Animal studies are essential for advancing our understanding of AD, identifying potential drug targets, and testing experimental therapies. An ideal animal model not only exhibits the same symptoms and pathological changes as a human disease but also follows the same sequence of pathological events. This review highlights the various inducing agents used to model AD in animals, such as streptozotocin, aluminium chloride, trimethyltin, lipopolysaccharide, scopolamine, and others, along with their underlying mechanisms. The outcomes of some studies that used such inducing agents to develop AD are discussed briefly. Among chemically induced models, streptozotocin and amyloid-beta are the most frequently used, while d-galactose, scopolamine, and aluminium-induced models are being used because they are non-invasive, reproducible, and compatible. However, none of the chemical/drug-induced models fully capture the scope of AD pathology and cognitive impairment. Overall, further research is necessary to establish the stability of the models in terms of consistency and reproducibility.

Information on the survival of urothelial cancer (UCa) patients with brain metastases (BM) is largely unreliable due to the rarity of such cases. Previous studies that have attempted to capture the prevalence and survival of these patients are limited to case series and retrospective studies with small cohort sizes. This study aimed to explore patient characteristics and treatment outcomes based on treatment modalities from a large sample of patients with UCa and BM.

In this retrospective study, we utilized the TriNetX Research Network, a real-world and in-house database with longitudinal electronic medical records from 92 institutions. The database was queried for patients with UCa who also had BM. Kaplan–Meier plots were used to assess overall survival (OS). Log-rank tests were applied for stratified outcomes. The Cox proportional hazards model was used for continuous data.

We identified 357 patients with UCa and BM, representing 4.7% of the 7,521 patients diagnosed with primary UCa. The mean age at diagnosis was 65.6 years, with a predominance of male patients (67%). The median OS from BM diagnosis was 18.6 months. For patients treated solely with stereotactic radiosurgery (SRS), the median OS was 20.8 months. For those treated with both SRS and surgical resection, the median OS was 18.6 months. There was no significant difference in survival between patients treated with SRS alone and those treated with both SRS and surgical resection (p = 0.875). For patients treated only with gemcitabine chemotherapy, the median OS was 15.4 months.

This study represents the largest known retrospective analysis of UCa patients with BM. Survival trends for patients treated with surgical resection, SRS, and systemic therapies are described in detail.

Breast cancer (BC) is the type of cancer with the highest incidence and mortality rates in women in the world. In the treatment of this neoplasia, several therapies are applied, including radiotherapy, hormonal therapy, chemotherapy, and biological therapy. Although most patients respond to these types of therapy, some patients over time, develop resistance or eventually relapse. Considering the above, future therapeutic concepts in BC are being directed at individualization of therapy and escalation of treatment based on tumor biology through the use of gene therapy. In this regard, a new genomic engineering technology, called the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-9 (Cas9), has acquired great importance in recent years, as a potential gene editing tool, extensively applied in human cancer research and cancer treatment. The aim of this review was to describe the advantages, limitations, and applications of CRISPR gene editing technology in BC treatment. Our review emphasizes the innovative facets and profound importance of CRISPR gene editing technology within the BC treatment landscape. Additionally, it provides valuable information to consider when evaluating the risks associated with the implementation of CRISPR-Cas9 technology in BC therapy.

Gastric cancer (GC) is a prevalent gastrointestinal malignancy, yet its early detection remains hindered due to the lack of available genetic markers. This study aimed to identify alternative genetic markers for the early prognosis and prevention of GC.

This objective was achieved through the analysis of differentially expressed genes (DEGs) from three datasets obtained from the Gene Expression Omnibus (GEO). By doing so, our goal was to identify hub genes associated with gastric adenocarcinoma that could serve as potential biomarkers for the early detection and management of GC. Three GEO datasets (GSE172032, GSE179581, and GSE181492), consisting of 10 normal and 10 GC samples were analyzed using the Galaxy web server. The visualizations of DEGs, including heatmaps, volcano plots, and MD plots, were generated via the same tool. ShinyGO performed Gene Ontology and KEGG enrichment analysis, while NetworkAnalyst identified a protein-protein interaction (PPI) network and screened 10 potential hub genes. Kaplan Meier plotter was used to analyze overall survival analysis for key hub genes, and NetworkAnalyst was used to assess protein-drug interactions for the top 10 hub genes.

A total of 1,079 common DEGs emerged across datasets, concentrating on significant GC-related pathways. Ten hub genes (H2BC21, H3C12, H2BC17, H3C2, H3C10, ERBB4, H2AC8, H3C8, H2BC14, and MAPT) were found to be linked to GC via PPI analysis. Survival analysis revealed that higher expression levels of ERBB4 and MAPT were associated with poor overall survival in GC patients. Furthermore, protein-drug interaction analysis revealed that the protein product of the MAPT gene exhibited a robust connection with drug compounds, specifically docetaxel and paclitaxel. These findings suggested that these drugs have the potential to inhibit the function of MAPT.

In summary, our findings provide putative candidate biomarkers, provide insights into GC treatment strategies, and highlight avenues for further research, contributing to a better understanding of the pathogenesis of GC.