Sonodynamic therapy for the treatment of atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease, stroke, and peripheral vascular disease. Despite the current treatments, mortality and disability still remain high. Sonodynamic therapy (SDT), a non-invasive and localized methodology, has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques. Promising progress has been made through cell and animal assays, as well as clinical trials. For example, the effect of SDT on apoptosis and autophagy of cells in AS, especially macrophages, and the concept of non-lethal SDT has also been proposed. In this review, we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS; we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages, T lymphocytes, neovascularization, smooth muscle cells, lipid, extracellular matrix and efferocytosis within plaques; additionally, we discuss the safety of SDT. A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

Establishment of a model of LPS-induced inflammatory injury in human aortic endothelial cells.

PURPOSE: We aim to establish an LPS-induced human aortic endothelial cells (HAECs) inflammatory injury model and explore the optimal conditions for inducing its injury. We expect to provide modeling references for the related experiments of vascular inflammatory diseases. METHODS: HAECs were cultured in vitro and treated with different concentrations of lipopolysaccharide (LPS) (0.1, 1, 10, 50, 100 µg/mL) for 6, 12, and 24 h to establish the HAECs inflammatory injury model. The cell viability was determined by CCK-8 assay; the expression levels of inflammatory cytokines in the cells were detected by RT-PCR；the apoptosis rate of the cells was detected by flow cytometry. RESULTS: ① Within 24 h of LPS treatment, the cell viability of the 0.1 and 1 µg/mL groups showed an overall increasing trend with time, while the cell viability of the 10, 50, and 100 µg/mL groups increased first and then decreased with time, and the cell viability of 50 and 100 µg/mL groups was significantly lower than the normal control group at 24 h (P<0.01). ② RT-PCR results showed that after 50 and 100 µg/mL LPS for 24 h, the inflammatory cytokines all showed an apparent upward trend compared with the normal control group (P<0.05), which was more significant in the 100 µg/mL group. ③ After 100 µg/mL LPS for 24 h, the apoptotic necrosis rate of HAECs was higher than the normal control group (P<0.01). CONCLUSIONS: This experiment successfully established a HAECs injury model, indicating that the optimal conditions for inducing injury are an LPS concentration of 100 µg/mL and a treatment time of 24 h.

iSMOD: an integrative browser for image-based single-cell multi-omics data.

Genomic and transcriptomic image data, represented by DNA and RNA fluorescence in situ hybridization (FISH), respectively, together with proteomic data, particularly that related to nuclear proteins, can help elucidate gene regulation in relation to the spatial positions of chromatins, messenger RNAs, and key proteins. However, methods for image-based multi-omics data collection and analysis are lacking. To this end, we aimed to develop the first integrative browser called iSMOD (image-based Single-cell Multi-omics Database) to collect and browse comprehensive FISH and nucleus proteomics data based on the title, abstract, and related experimental figures, which integrates multi-omics studies focusing on the key players in the cell nucleus from 20 000+ (still growing) published papers. We have also provided several exemplar demonstrations to show iSMOD's wide applications-profiling multi-omics research to reveal the molecular target for diseases; exploring the working mechanism behind biological phenomena using multi-omics interactions, and integrating the 3D multi-omics data in a virtual cell nucleus. iSMOD is a cornerstone for delineating a global view of relevant research to enable the integration of scattered data and thus provides new insights regarding the missing components of molecular pathway mechanisms and facilitates improved and efficient scientific research.

Effect of gut flora mediated-bile acid metabolism on intestinal immune microenvironment.

According to reports, gut microbiota and metabolites regulate the intestinal immune microenvironment. In recent years, an increasing number of studies reported that bile acids (BAs) of intestinal flora origin affect T helper cells and regulatory T cells (Treg cells). Th17 cells play a pro-inflammatory role and Treg cells usually act in an immunosuppressive role. In this review, we emphatically summarised the influence and corresponding mechanism of different configurations of lithocholic acid (LCA) and deoxycholic acid (DCA) on intestinal Th17 cells, Treg cells and intestinal immune microenvironment. The regulation of BAs receptors G protein-coupled bile acid receptor 1 (GPBAR1/TGR5) and farnesoid X receptor (FXR) on immune cells and intestinal environment are elaborated. Furthermore, the potential clinical applications above were also concluded in three aspects. The above will help researchers better understand the effects of gut flora on the intestinal immune microenvironment via BAs and contribute to the development of new targeted drugs.

Roles of cancer-associated fibroblasts (CAFs) in anti- PD-1/PD-L1 immunotherapy for solid cancers.

In recent years, breakthroughs have been made in tumor immunotherapy. However, tumor immunotherapy, particularly anti-PD-1/PD-L1 immune checkpoint inhibitors, is effective in only a small percentage of patients in solid cancer. How to improve the efficiency of cancer immunotherapy is an urgent problem to be solved. As we all know, the state of the tumor microenvironment (TME) is an essential factor affecting the effectiveness of tumor immunotherapy, and the cancer-associated fibroblasts (CAFs) in TME have attracted much attention in recent years. As one of the main components of TME, CAFs interact with cancer cells and immune cells by secreting cytokines and vesicles, participating in ECM remodeling, and finally affecting the immune response process. With the in-depth study of CAFs heterogeneity, new strategies are provided for finding targets of combination immunotherapy and predicting immune efficacy. In this review, we focus on the role of CAFs in the solid cancer immune microenvironment, and then further elaborate on the potential mechanisms and pathways of CAFs influencing anti-PD-1/PD-L1 immunotherapy. In addition, we summarize the potential clinical application value of CAFs-related targets and markers in solid cancers.

Ultrasound-targeted microbubble destruction remodels tumour microenvironment to improve immunotherapeutic effect.

Cancer immunotherapy (CIT) has gained increasing attention and made promising progress in recent years, especially immune checkpoint inhibitors such as antibodies blocking programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). However, its therapeutic efficacy is only 10-30% in solid tumours and treatment sensitivity needs to be improved. The complex tissue environment in which cancers originate is known as the tumour microenvironment (TME) and the complicated and dynamic TME is correlated with the efficacy of immunotherapy. Ultrasound-targeted microbubble destruction (UTMD) is an emerging technology that integrates diagnosis and therapy, which has garnered much traction due to non-invasive, targeted drug delivery and gene transfection characteristics. UTMD has also been studied to remodel TME and improve the efficacy of CIT. In this review, we analyse the effects of UTMD on various components of TME, including CD8+ T cells, tumour-infiltrating myeloid cells, regulatory T cells, natural killer cells and tumour vasculature. Moreover, UTMD enhances the permeability of the blood-brain barrier to facilitate drug delivery, thus improving CIT efficacy in vivo animal experiments. Based on this, we highlight the potential of immunotherapy against various cancer species and the clinical application prospects of UTMD.