Farnesoid X Receptor: Effective alleviation of rifampicin -induced liver injury.

Antituberculosis drugs induce pharmacologic cholestatic liver injury with long-term administration. Liver injury resulting from rifampicin is potentially related to the bile acid nuclear receptor Farnesoid X Receptor (FXR). To investigate this, cholestasis was induced in both wild-type (C57BL/6N) mice and FXR knockout (FXR-null) mice through administration of rifampicin (200 mg/kg) via gavage for 7 consecutive days. Compared with C57BL/6N mice, FXR-null mice exhibited more severe liver injury after rifampicin administration, characterized by enlarged liver size, elevated transaminases, and increased inflammation. Moreover, under rifampicin treatment, FXR knockout impairs lipid secretion and exacerbates hepatic steatosis. Significantly, the expression of metabolism molecules BSEP increased, while NTCP and CYP7A1 decreased following rifampicin administration in C57BL/6N mice, whereas these changes were absent in FXR knockout mice. Furthermore, rifampicin treatment in both C57BL/6N and FXR-null mice was associated with elevated c-Jun N-terminal kinase phosphorylation (p-JNK) levels, with a more pronounced elevation in FXR-null mice. Our study suggests that rifampicin-induced liver injury, steatosis, and cholestasis are associated with FXR dysfunction and altered bile acid metabolism, and that the JNK signaling pathway is partially implicated in this injury. Based on these results, we propose that FXR might be a novel therapeutic target for addressing drug-induced liver injury.

Bile acid-microbiota crosstalk in hepatitis B virus infection.

Hepatitis B virus (HBV) is a hepatotropic non-cytopathic virus characterized by liver-specific gene expression. HBV infection highjacks bile acid metabolism, notably impairing bile acid uptake via sodium taurocholate cotransporting polypeptide (NTCP), which is a functional receptor for HBV entry. Concurrently, HBV infection induces changes in bile acid synthesis and the size of the bile acid pool. Conversely, bile acid facilitates HBV replication and expression through the signaling molecule farnesoid X receptor (FXR), a nuclear receptor activated by bile acid. However, in HepaRG cells and primary hepatocytes, FXR agonists suppress HBV RNA expression and the synthesis and secretion of DNA. In the gut, the size and composition of the bile acid pool significantly influence the gut microbiota. In turn, the gut microbiota impacts bile acid metabolism and innate immunity, potentially promoting HBV clearance. Thus, the bile acid-gut microbiota axis represents a complex and evolving relationship in the context of HBV infection. This review explores the interplay between bile acid and gut microbiota in HBV infection and discusses the development of HBV entry inhibitors targeting NTCP.

The covariant structural and functional neuro-correlates of cognitive impairments in patients with end-stage renal diseases.

Introduction: Cognitive impairment (CI) is a common complication of end-stage renal disease (ESRD) that is associated with structural and functional changes in the brain. However, whether a joint structural and functional alteration pattern exists that is related to CI in ESRD is unclear. Methods: In this study, instead of looking at brain structure and function separately, we aim to investigate the covariant characteristics of both functional and structural aspects. Specifically, we took the fusion analysis approach, namely, multimodal canonical correlation analysis and joint independent component analysis (mCCA+jICA), to jointly study the discriminative features in gray matter volume (GMV) measured by T1-weighted (T1w) MRI, fractional anisotropy (FA) in white matter measured by diffusion MRI, and the amplitude of low-frequency fluctuation (ALFF) measured by blood oxygenation-level-dependent (BOLD) MRI in 78 ESRD patients versus 64 healthy controls (HCs), followed by a mediation effect analysis to explore the relationship between neuroimaging findings, cognitive impairments and uremic toxins. Results: Two joint group-discriminative independent components (ICs) were found to show covariant abnormalities across FA, GMV, and ALFF (all p < 0.05). The most dominant joint IC revealed associative patterns of alterations of GMV (in the precentral gyrus, occipital lobe, temporal lobe, parahippocampal gyrus, and hippocampus), alterations of ALFF (in the precuneus, superior parietal gyrus, and superior occipital gyrus), and of white matter FA (in the corticospinal tract and inferior frontal occipital fasciculus). Another significant IC revealed associative alterations of GMV (in the dorsolateral prefrontal and orbitofrontal cortex) and FA (in the forceps minor). Moreover, the brain changes identified by FA and GMV in the above-mentioned brain regions were found to mediate the negative correlation between serum phosphate and mini-mental state examination (MMSE) scores (all p < 0.05). Conclusion: The mCCA+jICA method was demonstrated to be capable of revealing covariant abnormalities across neuronal features of different types in ESRD patients as contrasted to HCs, and joint brain changes may play an important role in mediating the relationship between serum toxins and CIs in ESRD. Our results show the mCCA+jICA fusion analysis approach may provide new insights into similar neurobiological studies.

Scholar Metrics Scraper (SMS): automated retrieval of citation and author data.

Academic departments, research clusters and evaluators analyze author and citation data to measure research impact and to support strategic planning. We created Scholar Metrics Scraper (SMS) to automate the retrieval of bibliometric data for a group of researchers. The project contains Jupyter notebooks that take a list of researchers as an input and exports a CSV file of citation metrics from Google Scholar (GS) to visualize the group's impact and collaboration. A series of graph outputs are also available. SMS is an open solution for automating the retrieval and visualization of citation data.