No abstract

Pro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.

Acute myeloid leukemia (AML) is a deadly hematological malignancy with frequent disease relapse. The biggest challenge for AML therapy is the lack of methods to target and kill the heterogeneous leukemia cells, which lead to disease relapse. Here, we describe a near-infrared (NIR) fluorescent dye, IR-26, which preferentially accumulates in the mitochondria of AML cells, depending on the hyperactive glycolysis of malignant cell, and simultaneously impairs oxidative phosphorylation (OXPHOS) to exert targeted therapeutic effects for AML cells. In particular, IR-26 also exhibits potential for real-time monitoring of AML cells with an in vivo flow cytometry (IVFC) system. Therefore, IR-26 represents a novel all-in-one agent for the integration of AML targeting, detection, and therapy, which may help to monitor disease progression and treatment responses, prevent unnecessary delays in administering upfront therapy, and improve therapeutic efficiency to the residual AML cells, which are responsible for disease relapse.

No abstract

An ultrasensitive and rapid sandwich-type chemiluminescence immunoassay (CLIA) was developed for the clinical determination of human epididymis protein 4 (HE4) in human serum, using GoldMag nanoparticles as solid phase and acridinium ester (AE) as chemiluminescence system (GMP-CLIA). The process of AE labeling antibodies was systematically studied and evaluated. The effect of varies factors such as molar ratio of AE to antibodies, labeling time, and the components of elution buffer and trigger solution were optimized. Under the selected conditions, AE labeling experiments were successfully performed with the average labeling efficiency of 1.92 ± 0.08, and antibody utilization rate of 69.77 ± 1.19%. Antibody activity remained unchanged after labeling. The established GMP-CLIA method can detect HE4 in the range of 0.25–50 ng·mL−1 (10–2000 pM) with a detection limit of 0.084 ng·mL−1 (3.36 pM). The sensitivity has reached a high level, comparable with the current commercial detection kits. This proposed method has been successfully applied to the clinical determination of HE4 in 65 human sera. The results showed a good correlation with a clinical method, microplate-based chemiluminescence enzyme immunoassay (CLEIA), with the correlation coefficient of 0.9594.

STER is an effective and safe technique for the treatment of SMTs arising from the MP layer in the EGJ. Irregular shape and tumor diameter ≥20 mm are the reliable risk factors for en bloc resection failure.

No abstract

Background and Purpose There is an urgent but unmet need for mitigating radiation‐induced intestinal toxicity while radio sensitising tumours for abdominal radiotherapy. We aimed to investigate the effects of metformin on radiation‐induced intestinal toxicity and radiosensitivity of colorectal tumours. Experimental Approach Acute and chronic histological injuries of the intestine from mice were used to assess radioprotection and IEC‐6 cell line was used to investigate the mechanisms in vitro. The fractionated abdominal radiation model of HCT116 and HT29 tumour grafts was used to determine the effects on colorectal cancer. Key Results Metformin alleviated radiation‐induced acute and chronic intestinal toxicity by optimising mitophagy which was AMPK‐dependent. In addition, our data indicated that metformin increased the radiosensitivity of colorectal tumours with P53 mutation both in vitro and in vivo. Conclusion and Implications Metformin may be a radiotherapy adjuvant agent for colorectal cancers especially those carrying P53 mutation. Our findings provide a new strategy for further precise clinical trials for metformin on radiotherapy.