Protective effect of Tibetan medicine Qiwei Tiexie pills on liver injury induced by acetaminophen overdose: An integrated strategy of network pharmacology, metabolomics and transcriptomics.

BACKGROUND: Drug-induced liver injury, particularly from acetaminophen (APAP), has emerged as a significant public health concern. Unfortunately, there is currently no effective treatment strategy available. Qiwei Tiexie pills (QWTX), a traditional Tibetan medicine, have demonstrated considerable clinical efficacy in treating various liver diseases. Nevertheless, the protective effect of QWTX against drug-induced liver injury and its underlying mechanism remains poorly understood. PURPOSE: This study aimed to assess the therapeutic potential of QWTX, a Tibetan medicine, in an animal model of APAP-induced liver injury. Additionally, we sought to investigate the molecular mechanism through which QWTX exerts its effects. METHODS: We employed LC-MS and network pharmacology to predict the potential targets of QWTX in drug-induced liver injury. Subsequently, we employed HE staining, transcriptomics, metabolomics, and qRT-PCR to analyze the mechanism underlying QWTX treatment in drug-induced liver injury. RESULTS: Network pharmacology analysis revealed that the active components of QWTX are involved in inflammatory and drug metabolism-related pathways. In mouse models, pretreatment with QWTX effectively mitigated the elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory factors (IL-1ß, IL-6, and TNF-α) induced by APAP overdose. Moreover, APAP inhibited 1459 differentially expressed genes (DEGs) and 874 differential accumulation metabolites (DAMs), while QWTX promoted their expression. Conversely, APAP promoted 874 genes and 119 metabolites, which were inhibited by QWTX. Further analysis demonstrated that QWTX ameliorated the metabolic disorders induced by APAP overdose and potentially exerted a protective effect by inhibiting the expression of critical genes in crucial inflammatory pathways. QWTX also up-regulated antioxidant enzymes, thereby mitigating the oxidative stress resulting from APAP overdose. CONCLUSION: QWTX treatment effectively protects against APAP-induced liver damage in mice. Transcriptomic and metabolomic analyses further revealed that QWTX ameliorated hepatic metabolic disorders induced by APAP overdose while significantly suppressing the inflammatory response and oxidative stress associated with drug-induced liver injury. This study provides a new insight into the treatment of drug-induced liver injury by the TCM system and provides a basis for the development of new therapies for drug-induced liver injury by QWTX and its active ingredients.

Porous graphitic carbon nitride with high concentration of oxygen promotes photocatalytic H2 evolution.

Porous structure design and the content regulation of heteroelements have been proved to be effective strategies to boost photocatalytic H2 generation activity of graphitic carbon nitride (g-C3N4) based photocatalyst. Herein, a series of porous graphitic carbon nitride with high concentration of oxygen (g-C3N4-O) photocatalysts were synthesized via in situ polymerization process using colloidal SiO2 as oxygen source. The content of oxygen within the g-C3N4-O photocatalysts could be tuned by adjusting the amount of added colloidal SiO2 during the preparation procedure. The introduced oxygen replaced two-coordinated nitrogen atom, influencing band edge position and localized electron distribution, thereby enhancing visible light harvesting and photoelectric conversion. As a result, the g-C3N4-O photocatalyst with an optimal oxygen content (8.39 wt%) showed 10.5 fold enhancement in H2 evolution rate compared to that of bulk g-C3N4, attributed to the porous structure and high concentration of incorporated oxygen.

Effects of Osteocyte Shape on Fluid Flow and Fluid Shear Stress of the Loaded Bone.

This study was conducted to better understand the specific behavior of the intraosseous fluid flow. We calculated the number and distribution of bone canaliculi around the osteocytes based on the varying shapes of osteocytes. We then used these calculated parameters and other bone microstructure data to estimate the anisotropy permeability of the lacunar-canalicular network. Poroelastic finite element models of the osteon were established, and the influence of the osteocyte shape on the fluid flow properties of osteons under an axial displacement load was analyzed. Two types of boundary conditions (BC) that might occur in physiological environments were considered on the cement line of the osteon. BC1 allows free fluid passage from the outer elastic restraint boundary, and BC2 is impermeable and allows no free fluid passage from outer displacement constrained boundary. They both have the same inner boundary conditions that allow fluid to pass through. Changes in the osteocyte shape altered the maximum value of pressure gradient (PG), pore pressure (PP), fluid velocity (FV), and fluid shear stress (FSS) relative to the reference model (spherical osteocytes). The maximum PG, PP, FV, and FSS in BC2 were nearly 100% larger than those in BC1, respectively. It is found that the BC1 was closer to the real physiological environment. The fluid flow along different directions in the elongated osteocyte model was more evident than that in other models, which may have been due to the large difference in permeability along different directions. Changes in osteocyte shape significantly affect the degrees of anisotropy of fluid flow and porous media of the osteon. The model presented in this study can accurately quantify fluid flow in the lacunar-canalicular network.

Machine Learning Approach to Enhance the Performance of MNP-Labeled Lateral Flow Immunoassay.

The use of magnetic nanoparticle (MNP)-labeled immunochromatography test strips (ICTSs) is very important for point-of-care testing (POCT). However, common diagnostic methods cannot accurately analyze the weak magnetic signal from ICTSs, limiting the applications of POCT. In this study, an ultrasensitive multiplex biosensor was designed to overcome the limitations of capturing and normalization of the weak magnetic signal from MNPs on ICTSs. A machine learning model for sandwich assays was constructed and used to classify weakly positive and negative samples, which significantly enhanced the specificity and sensitivity. The potential clinical application was evaluated by detecting 50 human chorionic gonadotropin (HCG) samples and 59 myocardial infarction serum samples. The quantitative range for HCG was 1-1000 mIU mL-1 and the ideal detection limit was 0.014 mIU mL-1, which was well below the clinical threshold. Quantitative detection results of multiplex cardiac markers showed good linear correlations with standard values. The proposed multiplex assay can be readily adapted for identifying other biomolecules and also be used in other applications such as environmental monitoring, food analysis, and national security.

Dielectric properties of human liver from 10 Hz to 100 MHz: normal liver, hepatocellular carcinoma, hepatic fibrosis and liver hemangioma.

The dielectric properties of human liver were determined by characterization of tissue absorption and coupling of electromagnetic energy in the electromagnetic field. In this study the ex-vivo dielectric properties of human hepatocellular carcinoma (well and moderately differentiated), liver hemangioma, hepatic fibrosis (stages S1 and S2), and normal liver tissue were measured and analyzed over the frequency range of 10 Hz to 100 MHz. The dielectric properties over the frequency range can reflect tissue information including biological macromolecules, vesicles, and cellular membrane; these information aids in distinguishing different physiological states and lesions. The ex-vivo conductivity, permittivity, resistivity, as well as the characteristic parameters between the lesions and normal liver were analyzed and their differences were also verified. The data can contribute to developing bioelectric applications for tissue diagnostics and creating more accurate computer models for medical applications.

Reliability of in vivo measurements of the dielectric properties of anisotropic tissue: a simulative study.

A simulative study was performed to measure the dielectric properties of anisotropic tissue using several in vivo and in vitro probes. COMSOL Multiphysics was selected to carry out the simulation. Five traditional probes and a newly designed probe were used in this study. One of these probes was an in vitro measurement probe and the other five were in vivo. The simulations were performed in terms of the minimal tissue volume for in vivo measurements, the calibration of a probe constant, the measurement performed on isotropic tissue and the measurement performed on anisotropic tissue. Results showed that the in vitro probe can be used to measure the in-cell dielectric properties of isotropic and anisotropic tissues. When measured with the five in vivo probes, the dielectric properties of isotropic tissue were all measured accurately. For the measurements performed on anisotropic tissue, large errors were observed when the four traditional in vivo probes were used, but only a small error was observed when the new in vivo probe was used. This newly designed five-electrode in vivo probe may indicate the dielectric properties of anisotropic tissue more accurately than these four traditional in vivo probes.