Background Immune checkpoint blockade (ICB)-based cancer immunotherapy presents promising efficacy in cancer treatment. However, only a small portion of patients show responsiveness to the treatment, which is partially caused by limited tumor infiltration of T cells. Chemokines CXCL9, CXCL10 and CXCL11 bind to their receptor CXCR3 to regulate T cell invasion. Methods We delivered plasmids encoding CXCL9, CXCL10 and CXCL11 to tumor cells and tumor tissues using nanoparticles and investigated their effect on T cell invasion and infiltration. In addition, we applied these nanoparticles together with anti-PD-1 antibody, which is known to activate T cells and restore immune function against tumor cells. The anti-tumor effects were evaluated. Results Delivering plasmids encoding CXCL9, CXCL10 and CXCL11 by nanoparticles resulted in expression of these chemokines in both LLC cells and tumors. Expressing CXCL9, CXCL10 and CXCL11 promoted the infiltration of T cells in vitro and in vivo, as well as decreased the tumor size. Nanoparticles together with anti-PD-1 displayed the best anti-tumor effects. Conclusions Delivery of CXCL9/10/11 plasmids by nanoparticles promoted T cell infiltration in tumors and synergizes with the activity of anti-PD1 antibody.
Background Acute lung injury (ALI) caused by intestinal ischemia–reperfusion is a life-threatening disease. Interferon gene stimulator (STING) is a cytoplasmic DNA sensor that participates in the initiation of the inflammatory response. This study aims to establish whether C-176 (STING inhibitor) improves ALI under intestinal ischemia–reperfusion conditions. Methods To induce ALI, 72 male C57BL/6 mice were subjected to intestinal ischemia for 60 min and reperfusion for 3 h. Through intraperitoneal injection, C-176, a selective STING inhibitor, was injected 30 min before surgical treatment; meanwhile, compound C, an antagonist of adenosine monophosphate-activated protein kinase (AMPK), was administered 30 min after surgery. Based on immunofluorescence and Western blot assays, post-ALI assessments included lung water content (TLW), bronchoalveolar lavage fluid (BALF) protein, H&E staining, Masson staining, pulmonary pyroptosis [Gasdermin-D (GSDMD), cleaved caspase-1], and apoptosis (TUNEL, cleaved caspase-3). Results C-176 administration significantly attenuated intestinal ischemia–reperfusion-mediated ALI; this effect was reflected by exacerbated TLW and BALF protein, aggravated lung injury score, elevated degree of pulmonary fibrosis, increased TUNEL- and GSDMD-positive cells, and upregulated phospho-AMPK, cleaved caspase-1, cleaved caspase-3 and IFNβ mRNA expression. Moreover, C-176 increased phospho-AMPK under ALI conditions. Nonetheless, compound C partially reversed these beneficial effects. Conclusion C-176, a selective STING inhibitor, improves intestinal ischemia–reperfusion-mediated ALI, and its underlying mechanism may be associated with AMPK signal activation.
Six new compounds, xylomexicanins K-N (1-4), granasteroid (5) and 6-methoxy-2-pentylbenzofuran-4-ol (6), along with nine known compounds were isolated from the leaves and twigs of Xylocarpus granatum. Among them, 1 was a biogenetic precursor of 1,8,9-phragmalin limonoid, and 4 represent the first example of degraded A-ring limonoid. The structures of them were elucidated on the basis of one-and two-dimensional NMR spectroscopic data (including 1 H, 13 C-NMR, DEPT, 1 H-1 H COSY, HSQC, HMBC, and NOESY) and confirmed by high-resolution mass spectrometry.
Objective. To explore the effect of individual nursing combined with dietary management on blood glucose levels and quality of life in elderly patients with acute coronary syndrome with diabetes. Method. This study included 68 elderly patients who underwent acute coronary syndrome at Department of Emergency in our hospital from January 2018 to January 2020. And they were assigned to a control group (n = 34) treated with individual nursing and a research group (n = 34) treated with individual nursing and dietary management according to the random number table. A comparison of the changes in blood glucose levels, anxiety and depression, quality of life, and nursing satisfaction was made between groups before and after nursing. Result. Before nursing, the differences in blood glucose levels, SAS scores, and SDS scores between groups were not considered statistically significant ( P > 0.05 ). After nursing, the blood glucose levels, SAS, and SDS levels of patients in both groups significantly decreased, and the research group presented a higher decrease when compared with the control group ( P < 0.05 ). The short form health survey (SF-36) showed that the research group had higher scores in physical function (PF), general health (GH), vitality (VT), mental health (MH), social function (SF), role-physical (RP), bodily pain (BP), and role-emotional (RE) compared with the control group ( P < 0.05 ). The satisfaction survey presented that the research group had a significantly higher total score than the control group [(91.40 ± 5.23) vs. (86.61 ± 7.14), P < 0.05 ]. Conclusion. The combination of individual nursing and dietary management not only effectively reduces glycosylated hemoglobin levels and anxiety and depression but also wins better nursing satisfaction in the treatment of acute coronary syndrome in elderly patients. Moreover, their quality of life has been significantly improved after discharge.
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