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.

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.

Regulating cardiac differentiation to maintain normal heart development and function is very important. At present, biological functions of H19 in cardiac differentiation is not completely clear. To explore the functional effect of H19 during cardiac differentiation. Expression levels of early cardiac-specific markers Nkx-2.5 and GATA4, cardiac contractile protein genes α-MHC and MLC-2v were determined by qRT-PCR and western lot. The levels of lncRNA H19 and miR-19b were detected by qRT-PCR. We further predicted the binding sequence of H19 and miR-19b by online softwares starBase v2.0 and TargetScan. The biological functions of H19 and Sox6 were evaluated by CCK-8 kit, cell cycle and apoptosis assay and caspase-3 activity. The expression levels of α-MHC, MLC-2v and H19 were upregulated, and miR-19b was downregulated significantly in mouse P19CL6 cells at the late stage of cardiac differentiation. Biological function analysis showed that knockdown of H19 promoted cell proliferation and inhibits cell apoptosis. H19 suppressed miR-19b expression and miR-19b targeted Sox6, which inhibited cell proliferation and promoted apoptosis in P19CL6 cells during late-stage cardiac differentiation. Importantly, Sox6 overexpression could reverse the positive effects of H19 knockdown on P19CL6 cells. Downregulation of H19 promoted cell proliferation and inhibited cell apoptosis during late-stage cardiac differentiation by regulating the negative role of miR-19b in Sox6 expression, which suggested that the manipulation of H19 expression could serve as a potential strategy for heart disease.

Objectives: To analyze the association between global myocardial work indices evaluated by non-invasive left ventricular (LV) pressure-strain loop (PSL) and LV myocardial fibrosis in patients with dilated cardiomyopathy (DCM).Methods: A total of 57 patients with DCM were included in this prospective study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE) and global longitudinal strain (GLS) were measured using LVPSL. LV volumes and LV ejection fraction (LVEF) were evaluated using cardiac magnetic resonance imaging (CMRI), LV myocardial fibrosis was estimated at CMRI by qualitative assessment of late gadolinium enhancement (LGE). According to the CMRI, the studied population was divided into two groups, namely: patients without LGE (LGE-) and patients with LGE (LGE+).Results: The LGE+ group presented with increased age, LV end systolic volume (LVESV) index and reduced GWI, GCW, GWE, GLS, CMRI-derived LVEF (LVEF_CMRI), the differences between the two groups were statistically significant (P < 0.05). After correcting for age and LVESV index, LVEF_CMRI, GLS, GWI, GCW, and GWE retained independent associations with LV myocardial fibrosis. According to receiver operating characteristics (ROC) analysis, LVEF_CMRI, and GCW showed larger AUC and higher accuracy, sensitivity, and specificity than GLS, the accuracy of predicting LV myocardial fibrosis ranged from high to low as: LVEF_CMRI, GCW, GWE, GWI, and GLS.Conclusions: LVEF_CMRI, GWI, GCW, GWE, and GLS remained significant predictors of LV myocardial fibrosis. LVEF_CMRI, and GCW appeared to better predict LV myocardial fibrosis compared with GLS.

Background: Cardiac‐resident or ‐enriched microRNAs (miRNAs) could be released into the bloodstream becoming circulating cardiac miRNAs, which are increasingly recognized as non‐invasive and accessible biomarkers of multiple heart diseases. However, dilated cardiomyopathy (DCM)‐associated circulating miRNAs (DACMs) and their roles in DCM pathogenesis remain largely unexplored.Methods: Two human cohorts, consisting of healthy individuals and DCM patients, were enrolled for serum miRNA sequencing (10 vs. 10) and quantitative polymerase chain reaction validation (46 vs. 54), respectively. Rigorous screening strategy was enacted to define DACMs and their potentials for diagnosis. DCM mouse model, different sources of cardiomyocytes, adeno‐associated virus 9 (AAV9), gene knockout, RNAscope miRNA in situ hybridization, mRFP‐GFP‐LC3B reporter, echocardiography and transmission electron microscopy were adopted for mechanistic explorations.Results: Serum miRNA sequencing revealed a unique expression pattern for DCM circulating miRNAs. DACMs miR‐26a‐5p, miR‐30c‐5p, miR‐126‐5p and miR‐126‐3p were found to be depleted in DCM circulation as well as heart tissues. Their expressions in circulation and heart tissues were proven to be correlated significantly, and a combination of these miRNAs was suggested potential values for DCM diagnosis. FOXO3, a predicted common target, was experimentally demonstrated to be co‐repressed within cardiomyocytes by these DACMs except miR‐26a‐5p. Delivery of a combination of miR‐30c‐5p, miR‐126‐5p and miR‐126‐3p into the murine myocardium via AAV9 carrying an expression cassette driven by cTnT promoter, or cardiac‐specific knockout of FOXO3 (Myh6‐Cre^ERT2, FOXO3 flox^+/+) dramatically attenuated cardiac apoptosis and autophagy involved in DCM progression. Moreover, competitively disrupting the interplay between DACMs and FOXO3 mRNA by specifically introducing their interacting regions into murine myocardium crippled the cardioprotection of DACMs against DCM.Conclusions: Circulating cardiac miRNA‐FOXO3 axis plays a pivotal role in safeguarding against myocardial apoptosis and excessive autophagy in DCM development, which may provide serological cues for DCM non‐invasive diagnosis and shed light on DCM pathogenesis and therapeutic targets.

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.