Exploring the role and mechanism of Astragalus membranaceus and radix paeoniae rubra in idiopathic pulmonary fibrosis through network pharmacology and experimental validation.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic disease with an unclear etiology and no effective treatment. This study aims to elucidate the pathogenic mechanism networks involving multiple targets and pathways in IPF. Extracts and metabolites of Astragalus membranaceus (AM) and Radix paeoniae rubra (RPR), two well-known traditional Chinese medicines, have demonstrated therapeutic effects on IPF. However, the underlying mechanisms of AM and RPR remain unclear. Utilizing network pharmacology analysis, differentially expressed genes (DEGs) associated with IPF were obtained from the GEO database. Targets of AM and RPR were identified using the TCM Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction. A protein-protein interaction (PPI) network was subsequently constructed and analyzed using the STRING database and Cytoscape software. Gene ontology enrichment analysis and kyoto encyclopedia of genes and genomes analysis were conducted using Metascape. Additionally, a component-target-pathway network and a Sankey diagram were employed to identify the main active components, and molecular docking was performed between these components and proteins encoded by key targets. Finally, in vivo studies were conducted based on network pharmacology. A total of 117 common targets between DEGs of IPF and drug targets were identified and included in the PPI network, in which AKT1, MAPK3, HSP90AA1, VEGFA, CASP3, JUN, HIF1A, CCND1, PTGS2, and MDM2 were predicted as key targets. These 117 targets were enriched in the PI3K-AKT pathway, HIF-1 signaling pathway, apoptosis, and microRNAs in cancer. Astragaloside III, (R)-Isomucronulatol, Astragaloside I, Paeoniflorin, and ß-sitosterol were selected as the main active components. Docking scores ranged from - 4.7 to - 10.7 kcal/mol, indicating a strong binding affinity between the main active compounds and key targets. In vivo studies have indeed shown that AM and RPR can alleviate the pathological lung fibrotic damage caused by bleomycin treatment. The treatment with AM and RPR resulted in a reduction of mRNA levels for key targets AKT1, HSP90AA1, CASP3, MAPK3, and VEGFA. Additionally, the protein expression levels of AKT1, HSP90AA1, and VEGFA were also reduced. These results support the therapeutic potential of AM and RPR in ameliorating pulmonary fibrosis and provide insight into the molecular mechanisms involved in their therapeutic effects.

Preparation of temperature-responsive nanomicelles with AIE property as fluorescence probe for detection of Fe3+ and Fe2.

Temperature-responsive nanomicelles with aggregation induced emission (AIE) property were prepared by the host-guest complexation of ferrocene functionalized tetraphenyl (TPE-Fc) and ß-cyclodextrin-poly (N-isopropylacrylamide) (ß-CD-(PNIPAM)7). The AIE chromophore TPE-Fc bound to the hydrophobic cavity of cyclodextrin serves as the core of micelles, and temperature sensitive PNIPAM serves as the shell to give the micelles good solubility. The size of the nanomicelles is about 100 nm. At the excitation wavelength of 340 nm, the strongest fluorescent emission peak was 421 nm. The introduction of cyclodextrin star polymer increased the fluorescence intensity of nanomicelles, thus improving the recognition of probe to Fe3+ and Fe2+. The fluorescent probe can quickly detect Fe3+ and Fe2+ in water within 5 min even in the presence of various interfering ions. The detection limits of Fe3+ and Fe2+ were 1.04 µM and 0.78 µM, respectively in the range of 10-90 µM. The formation of complex between the probe and Fe3+/Fe2+ was supported by Job's plot. The probe was successfully applied to the detection of Fe3+and Fe2+ in actual water sample with a good recovery. In addition, a possible sensing mechanism for the interaction of iron ions with amide bond groups of nanomicelles was proposed.

Chitosan coated fluorescent mesoporous silica for the sensitive and selective detection of H2O2.

A novel turn-on fluorescent sensor for hydrogen peroxide (H2O2) was prepared from chitosan (CS) coating mesoporous silica nanoparticles (MSNs) loaded with 1-(4-Aminophenyl)-1,2,2-triphenylethene (TPE-NH2) and silver nanoparticles (AgNCs). The surface of MSNs was coated by CS as the gatekeeper and the template for loading of AgNCs. Because of the surface plasmon-enhanced energy transfer (SPEET), AgNCs effectively quenched the fluorescence emission of nanoparticles. In the presence of H2O2, AgNCs can be oxidized to Ag+, resulting in the recovery of fluorescence. This fluorescent sensor was characterized with respect to its chemical composition, morphological features and optical properties by means of FTIR, XRD, TGA, SEM, TEM, XPS, UV-Vis and fluorescence spectroscopy. The MSN/TPE-CS@Ag nanoparticles showed good sensitivity and selectivity for H2O2 even with various interfering ions and agents. Under optimized conditions, the detection limit for H2O2 was 0.64 µM in the rage of 1-300 µM. The feasibility of the practical application of this probe was confirmed by accurate quantitative of H2O2 in practical samples.

Antifungal CoAl layered double hydroxide ultrathin nanosheets loaded with oregano essential oil for cereal preservation.

Fungal infestation of cereals seriously affects human health and the economy. Protecting cereals from fungal infestation is meaningful. Therefore, safe and economical antifungal agents must be explored. Oregano essential oil (OEO) has broad-spectrum antifungal activity but is unstable and poorly water-dispersible. CoAl-LDH ultrathin nanosheets (CoAl-LDH UNs) are a biosafe carrier with peroxidase-like activity and good water dispersibility. A new nanocomposite was constructed by integrating OEO and CoAl-LDH UNs named OEO/CoAl-LDH UNs. The antifungal activity of OEO was improved for the synergetic effect of OEO and CoAl-LDH UNs. OEO/CoAl-LDH UNs showed excellent antifungal activity against Fusarium moniliforme, Fusarium graminearum and Aspergillus flavus. A polyvinyl alcohol film containing OEO/CoAl-LDH UNs was prepared as a food package and effectively inhibited fungal infestation on cereals. This work can provide some insights for the exploration of other new antifungal materials. The good biosafety of this antifungal material can be effectively applied to food packaging.

Current status of and barriers to the treatment of advanced-stage liver cancer in China: a questionnaire-based study from the perspective of doctors.

BACKGROUND: Liver cancer is a severe public health problem worldwide, and it creates a relatively higher disease burden in China than in the Western world. Despite achieving notable progress in China, potential differences in some aspects of medical services for liver cancer may persist across different regions and hospitals. This warrants serious consideration of the actual status of and barriers to liver cancer treatment. We intended to explore the present status of and obstacles in liver cancer treatment especially for advanced-stage liver cancer. METHODS: In February 2021, a national multicenter cross-sectional study was conducted among 1500 doctors from 31 provinces of mainland China using a self-administered online questionnaire. Participants completed the questionnaire about their general information, perspectives on the current status of liver cancer treatment, and expectations for future treatment. Chi-square and logistic regression analyses were performed to explore the differences associated with the regions, doctors' professional ranks, and hospital levels. RESULTS: Treatment conditions, medications, and treatment strategies were inconsistent across different economic regions and hospital of different levels. With respect to obstacles in treatment, 76.6% of the doctors were unsatisfied with the current treatment for liver cancer. Important factors that influenced their satisfaction with the treatment for liver cancer included early diagnosis and the disclosure of true conditions to patients. CONCLUSIONS: There persists differences in the treatment of liver cancer in China, besides barriers to treatment. More attention should be paid to the detection and treatment of liver cancer and the propagation of novel progress among doctors in underdeveloped areas.

Aggregation-Induced Emission (AIE) Photosensitizer Combined Polydopamine Nanomaterials for Organelle-Targeting Photodynamic and Photothermal Therapy by the Recognition of Sialic Acid.

The construction of organelle-targeting nanomaterials is an effective way to improve tumor imaging and treatment. Here, a new type of composite nanomaterial named as PTTPB is developed. PTTPB is composed of organelle-targeting aggregation-induced emission photosensitizer TTPB and polydopamine nanomaterials. With the functional modification of TTPB, PTTPB can recognize sialic acid on the cell membrane and present mitochondrial targeted capabilities. The intake of PTTPB in cancerous cells can be increased by the recognition process of cell membrane. PTTPB can generate singlet oxygen for photodynamic therapy (PDT), and present good photothermal conversion ability with irradiation. The PTTPB with organelle-targeting imaging-guided can realize the tumor ablation with the synergistic effect of PDT and photothermal therapy.

Phenylboronic-acid-based Functional Chemical Materials for Fluorescence Imaging and Tumor Therapy.

Various functional chemical materials have been widely used in imaging and tumor therapy. Targeted ligands such as antibodies, peptides, and small molecules have been combined with functional materials to enhance cellular uptake and are used for active targeting of cancer cells and tumors. Among them, phenylboronic acid (PBA), as a small molecular ligand, has the characteristics of low cytotoxicity and easy modification. PBA improves the cancer cell imaging and tumor treatment effect by binding to glycans on the surface of cancer cells. In this Mini-Review, we introduced the modification strategy and targeting strategy of PBA. We focused on the applications of PBA-based functional materials in fluorescence imaging and tumor therapy. For fluorescence imaging, the potential of PBA-based functional chemical materials in cancer diagnosis and tumor targeting was proved by cell imaging and in vivo imaging. For tumor therapy, we mainly discussed the applications of PBA-based functional chemical materials in chemotherapy, gene therapy, phototherapy, and immunotherapy. PBA-based functional chemical materials provide a useful method for cancer diagnosis and treatment.

Ubiquitination of non-lysine residues in the retroviral integrase.

Retroviral integrase catalyzes the integration of retroviral genome into host chromosomal DNA, which is a prerequisite of effective viral replication and infection. The human immunodeficiency virus type 1 (HIV-1) integrase has previously been reported to be regulated by the ubiquitination, but the molecular characterization of integrase ubiquitination is still unclear. In this study, we analyzed the ubiquitination of avian leukosis virus (ALV) integrase in detail. The ubiquitination assay showed that, like HIV-1, ALV integrase could also be modified by ubiquitination when expressed in 293 T and DF-1 cells. Domain mapping analysis revealed that the ubiquitination of ALV integrase might mainly occurred in the catalytic core and the N-terminal zinc-binding domains. Both lysine and non-lysine residues within integrase of ALV and HIV-1 were responsible for the ubiquitin conjugation, and the N-terminal HHCC zinc-binding motif might play an important role in mediating integrase ubiquitination. Interestingly, mass spectrometry analysis identified the Thr10 and Cys37 residues in the HHCC zinc-binding motif as the ubiquitination sites, indicating that ubiquitin may be conjugated to ALV integrase through direct interaction with the non-lysine residues. These findings revealed the detailed features of retroviral integrase ubiquitination and found a novel mechanism of ubiquitination mediated by the non-lysine residues within the N-terminal zinc-binding domain of integrase.

COP9 signalosome subunit 6 binds and inhibits avian leukosis virus integrase.

The retroviral integrase plays an essential role in the integration of reverse-transcribed retroviral cDNA into the host cell genome, and serves as an important target for anti-viral therapeutics. In this study, we identified the COP9 signalosome subunit 6 (CSN6) as a novel avian leukosis virus (ALV) integrase binding protein. Co-immunoprecipitation and GST pull-down assays showed that CSN6 bound to ALV integrase likely through direct interaction of CSN6 to the catalytic core of the integrase. We further demonstrated CSN6 inhibited integrase activity in vitro; knockdown of CSN6 in DF-1 promoted ALV production. These results indicated that CSN6 may be a negative regulator of ALV replication by binding to and inhibiting integrase. Our findings provided the insight into the integrase-based host defense system and may have implications in the development of integrase-based anti-viral strategies.