Engineered Enzyme-Loaded Erythrocyte Vesicles Precisely Deprive Tumoral Nutrients to Induce Synergistic Near-Infrared-II Photothermal Therapy and Immune Activation.

Starvation therapy has been considered a promising strategy in cancer treatment for altering the tumor microenvironment (TME) and causing a cascade of therapeutic effects. However, it is still highly challenging to establish a therapeutic strategy for precisely and potently depriving tumoral nutrition. In this study, a glucose oxidase (GOx) and thrombin-incorporated erythrocyte vesicle (EV) with cyclic (Arg-Gly-Asp) (cRGD) peptide modification, denoted as EV@RGT, were synthesized for precisely depriving tumoral nutrition and sequentially inducing second near-infrared region (NIR-II) photothermal therapy (PTT) and immune activation. The EV@RGT could specifically accumulate at the tumor site and release the enzymes at the acidic TME. The combination of GOx and thrombin exhausts tumoral glucose and blocks the nutrition supply at the same time, resulting in severe energy deficiency and reactive oxygen species (ROS) enrichment within tumor cells. Subsequently, the abundant clotted erythrocytes in tumor vessels present outstanding localized NIR-II PTT for cancer eradication owing to the hemoglobin. Furthermore, the abundant ROS generated by enhanced starvation therapy repolarizes resident macrophages into the antitumor M1 phenotype via a DNA damage-induced STING/NF-κB pathway, ultimately contributing to tumor elimination. Consequently, the engineered EV@RGT demonstrates powerful antitumor efficiency based on precise nutrition deprivation, sequential NIR-II PTT, and immune activation effect. This work provides an effective strategy for the antitumor application of enzyme-based reinforced starvation therapy.

A device-independent method for the colorimetric quantification on microfluidic sensors using a color adaptation algorithm.

A general and adaptable method is proposed to reliably extract quantitative information from smartphone images of microfluidic sensors. By analyzing and processing the color information of selected standard substances, the influence of light conditions, device differences, and human factors could be significantly reduced. Machine learning and multivariate fitting methods were proved to be effective for chroma correction, and a key element was the training of sample size and the fitting form, respectively. A custom APP was developed and validated using a high-sensitivity chromium ion quantification paper chip. The average chroma deviations under different conditions were reduced by more than 75% in RGB color space, and the concentration test error was reduced by more than half compared with the commonly used method. The proposed approach could be a beneficial supplement to existing and potential colorimetry-based detection methods.

Total flavonoids of Rhizoma drynariae promote angiogenesis and osteogenesis in bone defects.

Bone defects are difficult to heal, which conveys a heavy burden to patients' lives and their economy. The total flavonoids of Rhizoma drynariae (TFRD) can promote the osteogenesis of distraction osteogenesis. However, the dose effect is not clear, the treatment period is short, and the quality of bone formation is poor. In our study, we observed the long-term effects and dose effects of TFRD on bone defects, verified the main ingredients of TFRD in combination with network pharmacology for the first time, explored its potential mechanism, and verified these findings. We found that TFRD management for 12 weeks regulated osteogenesis and angiogenesis in rats with 4-mm tibial bone defects through the PI3K/AKT/HIF-1α/VEGF signaling pathway, especially at high doses (135 mg kg-1  d-1 ). The vascularization effect of TFRD in promoting human umbilical vein endothelial cells was inhibited by PI3K inhibitors. These results provide a reference for the clinical application of TFRD.

Exploring the treatment of COVID-19 with Yinqiao powder based on network pharmacology.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In China, Yinqiao powder is widely used to prevent and treat COVID-19 patients with Weifen syndrome. In this study, the screening and verification of active ingredients, target selection and DisGeNET scoring, drug-ingredient-gene network construction, protein-protein interaction network construction, molecular docking and surface plasmon resonance (SPR) analysis, gene ontology (GO) functional analysis, gene tissue analysis, and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to explore the active ingredients, targets, and potential mechanisms of Yinqiao powder in the treatment of COVID-19. We also predicted the therapeutic effect of Yinqiao powder using TCM anti-COVID-19 (TCMATCOV). Yinqiao powder has a certain therapeutic effect on COVID-19, with an intervention score of 20.16. Hesperetin, eriodictyol, luteolin, quercetin, and naringenin were the potentially effective active ingredients against COVID-19. The hub-proteins were interleukin-6 (IL-6), mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and tumor protein P53 (TP53). The potential mechanisms of Yinqiao powder in the treatment of COVID-19 are the TNF signaling pathway, T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and MAPK signaling pathway. This study provides a new perspective for discovering potential drugs and mechanisms of COVID-19.

Total Flavonoids of Rhizoma Drynariae Enhances Angiogenic-Osteogenic Coupling During Distraction Osteogenesis by Promoting Type H Vessel Formation Through PDGF-BB/PDGFR-ß Instead of HIF-1α/ VEGF Axis.

Background: Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney-tonifying traditional Chinese medicine Rhizoma Rrynariae, has been proved to be effective in treating osteoporosis, bone fractures and defects. However, pharmacological effects of TFRD on type H vessels, angiogenic-osteogenic coupling in distraction osteogenesis (DO) and the mechanism remain unclear. This study aims at investigating whether type H vessels exist in the DO model, effects of TFRD on angiogenic-osteogenic coupling and further elucidating the underlying mechanism. Methods: Rats models of DO and bone fracture (FR) were established, and then were separately divided into TFRD and control subgroups. Imageological and histological analyses were performed to assess bone and vessel formation. Immunofluorescent staining of CD31 and endomucin (Emcn) was conducted to determine type H vessel formation. Matrigel tube formation, ALP and Alizarin Red S staining assays were performed to test the effects of TFRD on angiogenesis or osteogenesis of endothelial precursor cells (EPCs) or bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, expression levels of HIF-1α, VEGF, PDGF-BB, RUNX2 and OSX were determined by ELISA, qPCR or western blot, respectively. Results: The in vivo results indicated more formed type H vessels in DO groups than in FR groups and TFRD obviously increased the abundance of type H vessels. Moreover, groups with higher abundance of type H vessels showed better angiogenesis and osteogenesis outcomes. Further in vitro experiments showed that TFRD significantly promoted while blocking PDGF-BB remarkably suppressed the angiogenic activity of EPCs under stress conditions. The levels of p-AKT and p-ERK1/2, downstream mediators of the PDGF-BB pathway, were up-regulated by TFRD but blocked by function blocking anti-PDGF-BB antibody. In contrast, the activated AKT and ERK1/2 and corresponding tube formation were not affected by the HIF-1α inhibitor. Besides, blocking PDGF-BB inhibited the osteogenic differentiation of the stretched BMSCs, but TFRD enhanced the osteogenic activity of BMSCs and ameliorated the inhibition, with more calcium nodes, higher ALP activity and mRNA and protein levels of RUNX2 and OSX. Conclusion: Type H vessels exist in the DO model and TFRD enhances angiogenic-osteogenic coupling during DO by promoting type H vessel formation via PDGF-BB/PDGFR-ß instead of HIF-1α/VEGF axis.

An integrated data filtering and identification strategy for rapid profiling of chemical constituents, with Arnebiae Radix as an example.

Profiling the chemical components of complicated herbal extracts using traditional analytical methods is time-consuming and laborious. In this study, an integrated data filtering and identification strategy was developed to efficiently identify the chemical constituents in Arnebiae Radix. The post-acquisition data processing steps with this strategy were as follows: (1) data acquisition by ultra-high performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-MS); (2) background subtraction on the basis of the total ion chromatogram (TIC) to obtain the background-subtracted ion chromatogram; (3) construction of a diagnostic ion database based on the measured MS/MS fragment ions of reference standards and auxiliary diagnostic information according to literatures; (4) mass defect filtering (MDF) to filter the background-subtracted ion chromatogram; and (5) rapid structural identification in the MDF-processed ion chromatogram on the basis of the diagnostic ion database and further structural confirmation by analysing the retention time, fragment behaviour, and online databases (Chemspider, PubChem, and SciFinder). In this study, the herbal medicine Arnebiae Radix was used to illustrate this strategy. A total of 96 compounds were efficiently exposed and characterized from Arnebiae Radix samples obtained from 20 sources, and 13 of these compounds were confirmed by comparison with the reference standards. Thirty components with a low abundance, that remained undetected in the TIC, were identified in the MDF-processed ion chromatogram. Nine of these compounds had not been identified from Arnebiae Radix previously, and were tentatively screened as unknowns. The chemical components in traditional Chinese medicine preparations are considered to be the material basis for the effectiveness of this medical system, and are closely related to the pharmacological activities of the drugs. The pharmacodynamics of these drugs are known to be influenced by the synergistic effects of various components. Therefore, comprehensive profiling of the chemical compositions of herbal extracts is essential for systematic elucidation of the pharmacodynamics of these medicines.