Macrophages can be reprogramming, such as the classical activated macrophage, M1 or alternative activated macrophages, M2 phenotype following the milieu danger signals, especially inflammatory factors. Macrophage reprogramming is now considered as a key determinant of disease development and/or regression. Experimental autoimmune myocarditis (EAM) is characterized by monocytes/macrophage infiltration, Th17 cells activation and inflammatory factors producing such as high mobility group box 1 (HMGB1). Whether infiltrated macrophages could be reprogramming in EAM? HMGB1 was associated with macrophage reprogramming? Our results clearly demonstrated that infiltrated macrophage was reprogrammed towards a proinflammatory M1-like phenotype and cardiac protection by monocytes/macrophages depletion or HMGB1 blockade in EAM; in vitro, HMGB1 facilitated macrophage reprogramming towards M1-like phenotype dependent on TLR4-PI3Kγ-Erk1/2 pathway; furthermore, the reprogramming M1-like macrophage promoted Th17 expansion. Therefore, we speculated that HMGB1 contributed EAM development via facilitating macrophage reprogramming towards M1-like phenotype except for directly modulating Th17 cells expansion.
Using TEM, keratocyte activation could still be observed after SMILE compared to after PRK procedure. Fewer cellular ultrastructural changes were seen after SMILE procedure. Unlike in PRK procedure, no damaged epithelium and endothelium were found after SMILE.
Abstract. Myeloid-derived suppressor cells (MDSCs) were originally described as a heterogeneous population of immature cells derived from myeloid progenitors with immune-suppressive functions in tumor-bearing hosts. In recent years, increasing number of studies have described various populations of myeloid cells with MDSC-like properties in murine models of cancer and autoimmune diseases. These studies have observed that the populations of MDSCs are increased during inflammation and autoimmune conditions. In addition, MDSCs can effectively suppress T cell responses and modulate the activity of natural killer cells and other myeloid cells. MDSCs have also been implicated in the induction of regulatory T cell production. Furthermore, these cells have the potential to suppress the autoimmune response, thereby limiting tissue injury. Myeloid regulatory cells (Mregs) are recently attracting increasing attention, since they function in proinflammatory and immune suppression in autoimmune diseases, as well as in various types of cancer. Currently, research focus is directed from MDSCs to Mregs in cancer and autoimmune diseases. The present study reviewed the suppressive roles of MDSCs in various autoimmune murine models, the immune modulation of MDSCs to T helper 17 lymphocytes, as well as the proinflammatory and immunosuppressive roles of Mregs in various types of cancer and autoimmune diseases.
Purpose Owing to the lack of effective biomarkers, triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes of breast cancer. Meanwhile, tremendous progress has been made to identify biomarkers for TNBC. However, limited number of biomarkers still restrain the specifically targeting outcomes against TNBC. Here, to solve the obstacle, we designed and synthesized a new type of biocompatible nanoparticles to amplify the targeting effects for TNBC theranostics. Methods To identify the biomarker of TNBC, the expression of intercellular adhesion molecule-1 (ICAM1) was assessed by real-time polymerase chain reaction and western blot among all subtypes of breast cancer and normal breast epithelium. Then, vesicular nanoparticles based on poly(ethylene glycol)-poly(ε-caprolactone) copolymers were prepared by the double emulsion method and modified with anti-ICAM1 antibodies through click chemistry to conjugate with related antigens on TNBC cell membranes and then loaded with magnetic resonance imaging (MRI) contrast agent gadolinium and chemotherapeutic drug doxorubicin. The targeting capability, diagnostic and therapeutic efficacy of this nanoparticle were validated through cell-based and tumor model-based experiments. Results ICAM1 was expressed significantly higher on TNBC than on other subtypes of breast cancer and normal breast epithelium in both mRNA and protein level. Theranostic nanoparticle modified with anti-ICAM1 was proved to be able to specifically target to TNBC in vitro experiments. Such theranostic nanoparticle also displayed enhanced diagnostic and therapeutic efficacy by specifically targeting capability and extending circulation time in tumor models. The biocompatibility and biosafety of this nanoparticle was also confirmed in vitro and in vivo. Conclusion Overall, this new nanoparticle has been demonstrated with effective therapeutic outcomes against TNBC, providing a promising theranostic approach for MRI-guided therapy of TNBC.
Background: The quantitative MR techniques developed rapidly, vary MR-biomarkers have shown the ability to assess the quality of articular cartilage. This study aimed to investigate the diagnostic efficacy of multi-parametric quantitative ultrashort echo time (UTE)-based MRI for evaluating human cartilage degeneration. Methods: Twenty fresh anterolateral femoral condyle samples were obtained from 20 patients (age, 58.8±6.6 years; 6 females) who underwent total knee arthroplasty due to primary osteoarthritis (OA). The samples were imaged using UTE-based magnetization transfer (UTE-MT), UTE-based adiabatic T1ρ (UTE-AdiabT1ρ), UTE-based T2* (UTE-T2*), and CubeQuant-T2 sequences. Cartilage degeneration was classified based on the OA Research Society International grade and polarized light microscopy (PLM) collagen organization score. Spearman's correlation analysis was used to determine the relationships between quantitative MRI biomarkers [UTE-MT ratio (UTE-MTR), UTE-AdiabT1ρ, UTE-T2*, and CubeQuant-T2], OA Research Society International grade, and PLM collagen organization score. The diagnostic efficacy of each MRI biomarker for the detection of mild cartilage degeneration was assessed using the area under the receiver operating characteristic (ROC) curve (AUC).Results: Of the quantitative MRI biomarkers, UTE-MTR had the strongest correlation with both OA Research Society International grade (r=-0.709, P<0.001) and PLM collagen organization score (r=0.579, P<0.001). The UTE-MTR and UTE-AdiabT1ρ values showed significant differences between the normal group and the mild degeneration group (P=0.047 and 0.015, respectively), while UTE-T2* and CubeQuant-T2 did not. The UTE-MTR values were 15.90%±1.06% and 14.59%±1.35% for normal and mildly degenerated cartilage, respectively. The UTE-AdiabT1ρ values were 40.19±2.87 and 42.6±2.26 ms for normal and mildly degenerated cartilage, respectively. ROC analysis showed that UTE-MTR (AUC =0.805, P=0.001, sensitivity =73.7%, specificity =89.5%) had the highest diagnostic efficacy for mild cartilage ^ ORCID: 0000-0002-2331-3486. 2 Shao et al. Cartilage evaluation using multi qUTE-MRI
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