Triple-negative breast cancer (TNBC) is aggressive, with high recurrence rates and poor prognosis. Paclitaxel (PTX) remains a key chemotherapeutic agent for TNBC, but its efficacy diminishes due to the emergence of drug resistance, largely driven by cancer stem-like cells (CSCs), vasculogenic mimicry (VM) formation and tumor immunosuppressive microenvironment (TIME). Pyruvate kinase M2 (PKM2) is highly expressed in TNBC, and is a potential target for TNBC treatment. In this study, we developed a biomimetic codelivery system using albumin nanoparticles (termed S/P NP) to co-encapsulate PTX and shikonin (SHK), a natural inhibitor of PKM2. By inhibiting PKM2, SHK suppressed β-Catenin signaling, thereby reversing CSC stemness and preventing VM formation. The S/P NP system exhibited tumor-targeting delivery effect and significantly inhibited TNBC growth and lung metastasis. Mechanistically, the treatment reversed epithelial-mesenchymal transition (EMT) and stem-like properties of TNBC cells, suppressed VM formation, and remodeled the TIME. It reduced immunosuppressive cells (M2 macrophages, MDSCs) while promoting anti-tumor immunity (M1 macrophages, dendritic cells, cytotoxic T cells, and memory T cells). This dual-action strategy holds promise for improving TNBC therapy by targeting CSCs, VM, and the immune microenvironment, and for overcoming PTX resistance and reducing metastasis.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective:To systematically analyze the registration status of clinical trials related to inflammatory bowel disease (IBD) in China Clinical Trial Registry (ChiCTR); To focus on the characteristics and shortcomings of TCM research; To provide data support and theoretical basis for optimizing clinical trial design and improving the quality of TCM research.Methods:The IBD-related clinical trials registered by ChiCTR from the establishment of the database to September 18, 2024 were retrieved. SPSS 26.0 software was used to analyze the frequency of research objects, registration time, registration area and institution, source of funds, research type and design scheme, random method and blind method, trial staging and research center, sample size, intervention measures and outcome indicators.Results:There were 317 clinical trials of IBD. Shanghai, Jiangsu, Beijing, Guangdong and Zhejiang accounted for 72.87% of the total number of registrations. Most of the registered projects were intervention studies (51.42%), 48 studies used blind method, and randomized controlled study was the main research design type. In the 68 clinical trials related to TCM, the intervention measures were divided into 4 categories, of which Chinese materia medica was the most (42 items); the sample size was the most in the intervention study, with a total of 6 787 cases; the total frequency of outcome indicators was 1 866 times, and the quality of life and mental health were the most (147 items).Conclusions:The number of registered IBD clinical trials is generally increasing, but there may be problems such as uneven distribution of regions and institutions, poor design of sample size, blind method and other research, and non-standard filling of registration information. In the research of TCM treatment of IBD, it is suggested to further strengthen the depth and breadth, especially the characteristic therapy of TCM.

OBJECTIVE To prepare patchouli oil enteric-coated dropping pills, evaluate its colon-targeted release behaviors and therapeutic potency against rat ulcerative colitis(UC). METHODS The single factor combined with response surface optimization method was used to screen matrix types and optimize preparation process parameters. Formula and thickness of Eudragit coating was selected based on dissolution tendency toward simulated intestinal fluids. Finally, colon targeting release behavior and the therapeutic effect of the preparation were assessed on the rat UC model induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS). RESULTS The optimal prescription of patchouli oil dropping pills was patchouli oil∶PEG6000∶PEG8000 ratio of 1∶1∶1; and the optimal condition for preparing patchouli oil pills was keeping nozzle temperature at 9 ℃, and dropping pills at the speed of 33 drops·min−1, with dropping distance set at 6 cm; the optimal ratio of Eudragit L100∶Eudragit S100 was 3∶7 for preferential release in simulate intestinal fluid over simulated gastric fluid. Compared with free patchouli oil, patchouli oil enteric-coated dropping pills significantly alleviated the pathological symptoms such as weight loss, hematochezia and colon shortening in rats; the expression of pro-inflammatory cytokines IL-6, IL-1β, and IL-23 in serum was significantly down-regulated and the expression of anti-inflammatory cytokines IL-10 and TGF-β1 was significantly up-regulated. The mRNA expression of Mucin-1 and Mucin-2 in colon tissue was significantly up-regulated and the mRNA expression of inflammatory cytokines IL-6, IL-1β, and TNF-α was significantly down-regulated. CONCLUSION The patchouli oil enteric-coated dropping pills have colon-targeted release ability and improve the anti-inflammatory effect of drugs.

Objective To investigate the proliferation inhibition effect induced by medicarpin in liver cancer cells and its mechanism.Methods HepG2,HCC-M,and Hep3B cell lines were used to investigate the impact of medicarpin on the proliferation and survival of liver cancer cells.Changes(50 μmol/L medicarpin)in cell morphology were observed by inverted microscope and the proliferative capacity of cells(12.5,25,50 μmol/L medicarpin)was assessed using colony formation assays.To explore the potential mechanisms of medicarpin,the Swiss Target Prediction database was used to predict its target proteins.Subsequently,protein-protein interaction networks were constructed using STRING and Cytoscape,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Flow cytometry assay was used to evaluate cell cycle progression,while Western blotting was performed to assess the expression levels of cell cycle-related proteins.Furthermore,the effects of medicarpin on different cell lines with various levels of p53 expression were compared to validate the role of p53 in medicarpin-induced cell cycle arrest in liver cancer cells.Results Morphological changes such as disrupted membrane integrity,nuclear shrinkage,and loss of intercellular connections were observed in liver cancer cells treated with medicarpin.Additionally,a significant decrease in cell numbers was evident at various concentrations(12.5,25,50 μmol/L),and colony formation assays indicated that medicarpin significantly inhibited the quantity of colonies formed by liver cancer cells(P<0.05).The network construction and functional enrichment analysis indicated that medicarpin targets are enriched in cell cycle regulatory signaling pathways.Flow cytometry result showed that medicarpin induced G2/M cell cycle arrest in HepG2 cells,accompanied by the accumulation of p53 protein and downregulation of the cell cycle regulator cdc2(P<0.05).However,the G2/M phase cell cycle arrest induced by medicarpin could be reversed by a p53 inhibitor.More importantly,medicarpin was unable to induce G2/M phase cell cycle arrest in Hep3B(p53-null)and p53 knockout HCT116 cells,consistently indicating the critical role of p53 in medicarpin-induced G2/M phase cell cycle arrest.Conclusion Medicarpin inhibits the proliferation of liver cancer cells,and its anticancer effect is related to p53-dependent G2/M cell cycle arrest.

Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microenvironment, posing formidable challenges for effective treatment. The disease is characterized by an altered glucose metabolism in macrophages, specifically an increase in aerobic glycolysis, which is linked to heightened inflammatory responses. This suggests that targeting macrophage metabolism could offer a new therapeutic avenue. In this study, we developed an immunometabolic intervention using quercetin (Q) encapsulated in bioadhesive mesoporous polydopamine (Q@MPDA) to treat periodontitis. Our results demonstrated that Q@MPDA could reprogram inflammatory macrophages to an anti-inflammatory phenotype (i.e., from-M1-to-M2 repolarization). In a murine periodontitis model, locally administered Q@MPDA reduced the presence of inflammatory macrophages, and decreased the levels of inflammatory cytokines (IL-1β and TNF-α) and reactive oxygen species (ROS) in the periodontium. Consequently, it alleviated periodontitis symptoms, reduced alveolar bone loss, and promoted tissue repair. Furthermore, our study revealed that Q@MPDA could inhibit the glycolysis of inflammatory macrophages while enhancing oxidative phosphorylation (OXPHOS), facilitating the shift from M1 to M2 macrophage subtype. Our findings suggest that Q@MPDA is a promising treatment for periodontitis via immunometabolic rewiring.

Objective To investigate the proliferation inhibition effect induced by medicarpin in liver cancer cells and its mechanism.Methods HepG2,HCC-M,and Hep3B cell lines were used to investigate the impact of medicarpin on the proliferation and survival of liver cancer cells.Changes(50 μmol/L medicarpin)in cell morphology were observed by inverted microscope and the proliferative capacity of cells(12.5,25,50 μmol/L medicarpin)was assessed using colony formation assays.To explore the potential mechanisms of medicarpin,the Swiss Target Prediction database was used to predict its target proteins.Subsequently,protein-protein interaction networks were constructed using STRING and Cytoscape,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Flow cytometry assay was used to evaluate cell cycle progression,while Western blotting was performed to assess the expression levels of cell cycle-related proteins.Furthermore,the effects of medicarpin on different cell lines with various levels of p53 expression were compared to validate the role of p53 in medicarpin-induced cell cycle arrest in liver cancer cells.Results Morphological changes such as disrupted membrane integrity,nuclear shrinkage,and loss of intercellular connections were observed in liver cancer cells treated with medicarpin.Additionally,a significant decrease in cell numbers was evident at various concentrations(12.5,25,50 μmol/L),and colony formation assays indicated that medicarpin significantly inhibited the quantity of colonies formed by liver cancer cells(P<0.05).The network construction and functional enrichment analysis indicated that medicarpin targets are enriched in cell cycle regulatory signaling pathways.Flow cytometry result showed that medicarpin induced G2/M cell cycle arrest in HepG2 cells,accompanied by the accumulation of p53 protein and downregulation of the cell cycle regulator cdc2(P<0.05).However,the G2/M phase cell cycle arrest induced by medicarpin could be reversed by a p53 inhibitor.More importantly,medicarpin was unable to induce G2/M phase cell cycle arrest in Hep3B(p53-null)and p53 knockout HCT116 cells,consistently indicating the critical role of p53 in medicarpin-induced G2/M phase cell cycle arrest.Conclusion Medicarpin inhibits the proliferation of liver cancer cells,and its anticancer effect is related to p53-dependent G2/M cell cycle arrest.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a major health burden in the world. So far, many strategies have been investigated to control the spread of COVID-19, including social distancing, disinfection protocols, vaccines, and antiviral treatments. Despite the significant achievement, due to the constantly emerging new variants, COVID-19 is still a great challenge to the global healthcare system. It is an urgent demand for the development of new therapeutics and technologies for containing the wild spread of SARS-CoV-2. Inhaled administration is useful for the treatment of lung and respiratory diseases, and enables the drugs to reach the site of action directly with benefits of decreased dose, improved safety, and enhanced patient compliance. Nanotechnology has been extensively applied in the prevention and treatment of COVID-19. In this review, the inhaled nanomedicines and antibodies, as well as intranasal nanodrugs, for the prevention and treatment of COVID-19 are summarized.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.004.].

The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.