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Purpose: To evaluate the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using 99mTc-labeled C2A domain of synaptotagmin I in a mouse model., Materials and Methods: H460 tumor-bearing mice were treated with intravenous paclitaxel, and 12, 24, 48 and 72 h later, 99mTc-C2A-GST was injected intravenously, and planar images were acquired at 2, 4 and 6 h postinjection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and reflected specific binding of 99mTc-C2A-GST. Mice were sacrificed after 6-h imaging; caspase-3 as apoptosis executer was determined by flow cytometry; DNA fragmentation was analyzed by terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Whereas nonspecific accumulation was estimated using inactivated C2A-GST. The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity., Results: T/NT significantly increased after paclitaxel inducement, whereas it was low in untreated tumors (T/NT=1.24+/-0.23). In terms of % ID/g, activity in Group 2 (12 h), Group 3 (24 h), Group 4 (48 h) and Group 5 (72 h) after the treatment was 2.05+/-0.20, 3.02+/-1.01, 3.17+/-1.16 and 3.96+/-1.72, respectively. Whereas in the nontreated group, Group 1 % ID/g was 1.21+/-0.51. The radiotracer uptake was positively correlated to the apoptotic index (r=0.70, P<.01), as well as caspase-3 activity (r=0.75, P<.01)., Conclusion: This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using 99mTc-labeled C2A.

Periodontitis is an oral inflammatory disease characterised by the destruction of periodontal soft tissue and alveolar bone resorption, mainly triggered by plaque microbial infection. Pyroptosis is an inflammatory form of programmed cell death mediated by the pore‐forming gasdermin proteins, which resist the invasion of pathogens into the body's immune system. Many studies have found that pyroptosis is closely related to the occurrence and development of periodontitis. At present, most of these studies focused on the canonical pathway mediated by caspase‐1. Moreover, Gram‐negative bacteria's lipopolysaccharide has been shown to activate a new form of the non‐canonical inflammasome by directly binding to human caspase‐4/5 and mouse caspase‐11 in the cytosol. However, most of the functions of non‐canonical inflammasome are still gradually being studied. Therefore, in this review, we have summarised and analysed the existence and regulation mechanism of the non‐canonical inflammasome in periodontitis. [ABSTRACT FROM AUTHOR]

Background: Growth differentiation factor (GDF) acted as a factor that regulated proliferation, apoptosis and differentiation in several tumors. However, the effects of growth differentiation factor (GDF11) in pancreatic cancer remain unclear.Purpose: To investigate the expression and significance of GDF11 in pancreatic cancer.Patients and methods: Pancreatic cancer and corresponding paracancerous tissues (n=28) were collected from the Department of Hepatobiliary and Pancreatic Surgical Oncology of Chinese PLA General Hospital. Tissue microarray was obtained from Outdo Biotech Co., Ltd. (Shanghai, People's Republic of China). GDF11 mRNA and protein expressions in pancreatic cancer samples and cell lines were detected using qRT-PCR, Western-Blot and immunohistochemistry. Overexpression and knockdown of GDF11 were performed with lentiviral transduction system and siRNA technique in PANC-1 cell line and CFPAC-1 cell line. Proliferation, migration and invasion of pancreatic cancer cell lines were examinated by MTS and transwell assay, respectively. Flow cytometry was used for cell apoptosis analysis.Results: The results of this study indicated that GDF11 was significantly down-regulated in pancreatic cancer tissues compared with adjacent tissues of pancreatic cancer. GDF11 was also associated with low expression in pancreatic cancer cell lines when compared with normal pancreatic cell line. In a cohort of 63 pancreatic cancer patients, high GDF11 expression levels was associated with favorable perineural invasion, T classification, N classification and overall survival (OS). Cox proportional hazards model revealed that high GDF11 expression was an independent predictor of favorable prognosis (HR: 0.496; 95% CI: 0.255–0.967; P=0.040). Overexpression of GDF11 in PANC-1 cells repressed the proliferation, migration and invasion abilities in vitro. Inhibition of GDF11 in CFPAC-1 showed inverse results. Furthermore, enhanced GDF11 expression promoted apoptosis and down-regulated GDF11 expression inhibited apoptosis in pancreatic cancer cell lines. Conclusion: These findings suggested that GDF11 acted as a tumor suppressor gene for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The goal of this study was to evaluate the feasibility of 99mTc-His10-annexin V for the detection of acute myocardial cell death and to assess the effect of adenosine preconditioning in a porcine model of myocardium ischemia and reperfusion injury (RI). Materials and Methods: 99mTc-His10-annexin V was prepared by one-step direct labeling, and RCP and radiostability were tested. The binding of 99mTc-His10-annexin V to apoptosis was validated in vitro using camptothecin-induced Jurkat cells. In vivo biodistribution was determined in mice by the dissection method. Ischemia of 20–30 min was induced by balloon occlusion of the epicardial coronary artery of the porcine model (n=14). Adenosine was infused intravenously in six pigs before coronary occlusion. 99mTc-His10-annexin V (n=12) was injected intravenously at 1 h after reperfusion. SPECT/CT was acquired at 3 h postinjection. Myocardial perfusion imaging (MPI) with 99mTc-MIBI was also performed 1 day after His10-annexin V imaging. Cardiac tissues were analyzed postmortem using hematoxylin-and-eosin and TUNEL staining. Caspase-3 activity was measured to confirm the presence of apoptosis. Results: 99mTc-His10-annexin V had a RCP >98% and high stability 2 h after radiolabeling; it could bind to apoptotic cells with high affinity. Biodistribution of 99mTc-His10-annexin V showed a predominant uptake in the kidney and relatively low uptake in the myocardium, liver and gastrointestinal tract; rapid clearance from blood and kidney was observed. In the untreated group, intense uptake of His10-annexin V was visualized in the defect which was shown in MPI, whereas in the adenosine group a mild uptake of 99mTc-His10-annexin was found in the risk area which showed no defects in the 99mTc-MIBI image. TUNEL staining and activated caspase-3 confirmed the ongoing apoptosis in RI. Adenosine preconditioning significantly diminished the level of apoptosis. Uptake of His10-annexin V in RI correlated with TUNEL-positive nuclei. Conclusion: This study addresses the feasibility of imaging of myocardial cell death in acute ischemia and RI in pigs with 99mTc-His10-annexin V; it holds prospect for the detection of myocardial cell death in clinical practice. Adenosine preconditioning could attenuate the myocardial apoptosis; its cardioprotective effect might partially be fulfilled by suppressing the ongoing apoptosis in ischemia and reperfusion. Further study is warranted. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using 99mTc-labeled C2A domain of synaptotagmin I in a mouse model. Materials and Methods: H460 tumor-bearing mice were treated with intravenous paclitaxel, and 12, 24, 48 and 72 h later, 99mTc-C2A-GST was injected intravenously, and planar images were acquired at 2, 4 and 6 h postinjection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and reflected specific binding of 99mTc-C2A-GST. Mice were sacrificed after 6-h imaging; caspase-3 as apoptosis executer was determined by flow cytometry; DNA fragmentation was analyzed by terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Whereas nonspecific accumulation was estimated using inactivated C2A-GST. The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity. Results: T/NT significantly increased after paclitaxel inducement, whereas it was low in untreated tumors (T/NT=1.24±0.23). In terms of % ID/g, activity in Group 2 (12 h), Group 3 (24 h), Group 4 (48 h) and Group 5 (72 h) after the treatment was 2.05±0.20, 3.02±1.01, 3.17±1.16 and 3.96±1.72, respectively. Whereas in the nontreated group, Group 1 % ID/g was 1.21±0.51. The radiotracer uptake was positively correlated to the apoptotic index (r=0.70, P<.01), as well as caspase-3 activity (r=0.75, P<.01). Conclusion: This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using 99mTc-labeled C2A. [Copyright &y& Elsevier]