Yagang Song

Background: Pulmonary fibrosis (PF) is an interstitial lung disease with macrophage polarization playing a critical role. Previous research has demonstrated that essential oil from Radix Curcumae (RCEO) significantly ameliorates pulmonary sarcoidosis, an effect attributed to the modulation of macrophage polarization. However, the therapeutic potential of RCEO in PF and its underlying mechanisms remain to be elucidated. Purpose: To investigate whether RCEO ameliorates pulmonary function in PF mice by suppressing the polarization of M1 and M2 macrophages via suppressing the Pi3k/Akt/β-catenin and Tlr4/Myd88/Nf-κb signaling pathways. Methods: Bioinformatics and network pharmacology approaches were employed to predict the potential therapeutic targets of RCEO for PF. The main components of RCEO and the primary constituents of RCEO deposited in lung tissue following inhalation were analyzed using GC–MS. PF models were established both in vivo and in vitro using bleomycin. Changes in pulmonary function were assessed by whole-body plethysmography. HE staining and Masson staining were used to observe histopathological alterations and fibrosis progression in lung tissues. ELISA was performed to measure changes in fibrosis-related mediators in blood. Flow cytometry was utilized to investigate macrophage polarization and apoptosis levels in lung tissues. Immunofluorescence analysis was applied to quantify the expression and distribution of Tlr4 and Pi3k, as well as their fluorescence co-localization with macrophages, in lung tissues. PCR and WB were conducted to evaluate changes in mRNA expression levels and protein abundance associated with the Tlr4/Myd88/Nf-κb and Pi3k/Akt/β-catenin signaling pathways in lung tissues. Results: Bioinformatics and Network Pharmacology analyses predicted that the therapeutic effect of RCEO on PF is associated with the modulation of macrophage differentiation via the Tlr4/Myd88/Nf-κb pathway and the Pi3k/Akt/β-catenin signaling pathway. In a PF mouse model, RCEO significantly alleviated pathological alterations and collagen deposition in lung tissues and improved pulmonary function. Results from both in vivo and in vitro flow cytometry demonstrated that RCEO concurrently suppressed the differentiation of macrophages into both M1 and M2 phenotypes, promoted apoptosis in 3T3 cells while inhibiting apoptosis in MLE-12 cells, and reduced the levels of profibrotic mediators. Further PCR and Western blot analyses indicated that RCEO modulates macrophage polarization and extracellular matrix expression by inhibiting the Tlr4/Myd88/Nf-κb and Pi3k/Akt/β-catenin signaling pathways. Immunofluorescence assays revealed that RCEO effectively downregulated the expression of Tlr4 and Pi3k in macrophages, thereby exerting a protective effect against pulmonary fibrosis. Conclusion: RCEO ameliorates PF by suppressing both M1 and M2 polarization of macrophages via inhibition of the Pi3k/Akt/β-catenin and Tlr4/Myd88/Nf-κb signaling pathways. This leads to reduced release of pro-inflammatory and pro-fibrotic cytokines, decreased extracellular matrix (ECM) deposition, and overall attenuation of fibrotic progression.

Objective: The aim of this study is to investigate the recurrence and progression of liver cancer by focusing on the energy metabolism of liver cancer stem cells. Methods: A comprehensive literature search was conducted using databases including CNKI, PubMed, Wanfang, and Citexs to analyze the etiology and treatment of hepatocellular carcinoma (HCC), the factors and mechanisms contributing to HCC recurrence, and the impact of energy metabolism in HCC stem cells on the development of HCC. Furthermore, the association between HCC recurrence and the energy metabolism of HCC stem cells was examined. Results: The primary targets associated with the glycolytic metabolism of HCC stem cells included HK2, PFK, PK, LDH, among others. Glutamine metabolism primarily involves the tricarboxylic acid (TCA) cycle, with main targets such as mTORC1 and reactive oxygen species (ROS). The principal pathway in lipid metabolism is fatty acid (FA) biosynthesis, with key targets being fatty acid synthase (FASN), acetyl-coenzyme A carboxylase (ACC), stearoyl-coenzyme A desaturase-1 (SCD1), and adenosine monophosphate-activated protein kinase (AMPK). Targets in the oxidative phosphorylation pathway include PGC1a. Finally, key targets in iron metabolism encompass System Xc, glutathione peroxidase 4 (GPX4), and DMT1. Conclusion: The glycolytic metabolism of HCC stem cells represents a primary metabolic pathway in HCC stem cells, with key targets including HK2, PFK, PK, and LDH warranting closer attention. Glutamine metabolism should focus on the TCA cycle and targets such as mTORC1 and ROS. Lipid metabolism pathway involves FA biosynthesis, with significant targets being FASN, ACC, SCD1, and AMPK. Iron metabolism, specifically System Xc, GPX4, and DMT1 targets, should be carefully considered. Therefore, interventions for the prevention and treatment of liver cancer recurrence should be directed towards these aspects of liver cancer stem cells.

A series of co-crystals of ascorbic acid were prepared with equimolar amounts of co-crystal formers (CCFs), including isonicotinic acid, nicotinic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid and m-hydroxybenzoic acid, by slow solvent evaporation and solvent-assisted grinding. The co-crystals were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Molecular dynamics (MD) simulations further validated the interaction energy and the possible intermolecular hydrogen bonds among VC and CCFs. The co-crystals showed improved stability when exposed to different wavelengths of light, pH and temperatures compared to the free analogue, especially at higher pH (~9) and lower temperature (~4 °C).

The chemical constituents of Scutellaria baicalensis flower are flavonoids, volatile oils and melanin, It has anti-tumor, anti-inflammatory, antioxidant, anti angiogenic and antithrombotic pharmacological effects, and it has the effect of clearing away heat and relieving lung fire. Scutellaria baicalensis flower is rich in resources, cheap, easy to obtain, accurate effect, With the prevention and treatment of a variety of diseases. In this paper, the ancient application, chemical constituents, pharmacological actions and comprehensive utilization of Scutellaria baicalensis flower were reviewed, The purpose of this study was to explore the value of its development and utilization, so as to provide reference for the comprehensive utilization of Scutellaria baicalensis flower.

Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.