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6′-O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from peony root, has been proven to possess antioxidant potential. In this present study, we revealed that GPF treatment exerted significant neuroprotection of PC12 cells following OGD, as evidenced by a reduction of oxidative stress, inflammatory response, cellular injury, and apoptosis in vitro. Furthermore, treatment with GPF increased the levels of phosphorylated Akt (p-Akt) and nuclear factor-erythroid 2-related factor 2 (Nrf2), as well as promoted Nrf2 translocation in PC12 cells, which could be inhibited by Ly294002, an inhibitor of phosphoinositide 3-kinase (PI3K). In addition, Nrf2 knockdown or Ly294002 treatment significantly attenuated the antioxidant, anti-inflammatory, and antiapoptotic activities of GPF in vitro. In vivo studies indicated that GPF treatment significantly reduced infarct volume and improved neurological deficits in rats subjected to CIRI, as well as decreased oxidative stress, inflammation, and apoptosis, which could be inhibited by administration of Ly294002. In conclusion, these results revealed that GPF possesses neuroprotective effects against oxidative stress, inflammation, and apoptosis after ischemia-reperfusion insult via activation of the PI3K/Akt/Nrf2 pathway

Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Oncolytic virotherapy is an attractive drug platform of cancer gene therapy, but efficacy and specificity are important prerequisites for success of such strategies. Previous studies determined that Apoptin is a p53 independent, bcl-2 insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. Here, we generated a conditional replication-competent adenovirus (CRCA), designated Ad-hTERT-E1a-Apoptin, and investigated the effectiveness of the CRCA a gene therapy agent for further clinical trials.</p> <p>Results</p> <p>The observation that infection with Ad-hTERT-E1a-Apoptin significantly inhibited growth of the melanoma cells, protecting normal human epidermal melanocytes from growth inhibition confirmed cancer cell selective adenoviral replication, growth inhibition, and apoptosis induction of this therapeutic approach. The <it>in vivo </it>assays performed by using C57BL/6 mice containing established primary or metastatic tumors expanded the <it>in vitro </it>studies. When treated with Ad-hTERT-E1a-Apoptin, the subcutaneous primary tumor volume reduction was not only observed in intratumoral injection group but in systemic delivery mice. In the lung metastasis model, Ad-hTERT-E1a-Apoptin effectively suppressed pulmonary metastatic lesions. Furthermore, treatment of primary and metastatic models with Ad-hTERT-E1a-Apoptin increased mice survival.</p> <p>Conclusions</p> <p>These data further reinforce the previously research showing that an adenovirus expressing Apoptin is more effective and advocate the potential applications of Ad-hTERT-E1a-Apoptin in the treatment of neoplastic diseases in future clinical trials.</p

Isoliquiritigenin Activates Nuclear Factor Erythroid-2 Related Factor 2 to Suppress the NOD-Like Receptor Protein 3 Inflammasome and Inhibits the NF-κB Pathway in Macrophages and in Acute Lung Injury

Among the cellular response mechanisms, the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway is considered a survival pathway that alleviates oxidative injury, while both the NOD-like receptor protein 3 (NLRP3) and NF-κB pathways are pro-inflammatory pathways that cause damage to cells. These pathways are implicated in the development and resolution of acute lung injury (ALI). Isoliquiritigenin (ISL), a flavonoid from the liquorice compound, is suggested to be a regulator of the above pathways, but the mechanisms of how the NLRP3/NF-κB pathway interacts with Nrf2 and its protective effects in ALI remain unknown. In the present study, ISL inhibited reactive oxygen species (ROS) generation and cytotoxicity induced by t-BHP and pro-inflammatory enzymes production induced by LPS in RAW 264.7 cells. Such cytoprotective effects coincided with the induction of AMP-activated protein kinase (AMPK)/Nrf2/antioxidant response element (ARE) signaling and the suppression of the NLRP3 and NF-κB pathways. Consistent with these findings, ISL treatment significantly alleviated lung injury in LPS-induced ALI mice, which was reflected by reductions in histopathological changes, pulmonary edema, and protein leakage. At the same time, the increased levels of inflammatory cell exudation and pro-inflammatory mediators, the enhanced production of ROS, myeloperoxidase, and malondialdehyde, and the depleted expression of GSH and superoxide dismutase induced by LPS were ameliorated by ISL. Furthermore, ISL notably activated AMPK/Nrf2/ARE signaling and inhibited LPS-induced NLRP3 and NF-κB activation in the lung. Moreover, although inhibition of the LPS-induced histopathological changes and ROS production were attenuated in Nrf2-deficient mice, the repression of the NLRP3 and NF-κB pathways by ISL was Nrf2-dependent and Nrf2-independent, respectively. In conclusion, our results are the first to highlight the beneficial role and relevant mechanisms of ISL in LPS-induced ALI and provide novel insight into its application

Association of clinical stages of lung cancer with ThinPrep.

<p>SCC, squamous cell carcinoma; ADC, adenocarcinoma; SCLC, small cell lung carcinoma.</p

Cytomorphology of lung squamous cell carcinoma (SCC) using ThinPrep bronchial brushing cytology.

<p>Small clusters of malignant cells with features of poorly differentiated carcinoma. (A), Well-differentiated SCC. Cytological features are characterized by individual cells or cohesive sheets of tumor cells with clear cell borders and a dense cytoplasm. (B), Poorly differentiated SCC. Cytology shows high cellularity and small groups of tumor cells. The nuclear/cytoplasmic (N/C) ratio was usually high (Papanicolaou staining; the original magnification was 400×).</p

Cytomorphology of lung adenocarcinoma (ADC) in ThinPrep bronchial brushing cytology.

<p>(A and B), Typical features of ADC in cytology include cellular clusters with a deep focus due to the three-dimensional clusters of large vacuolated cells. Sometimes, the individual cells or acinar (glandular) arrangements were visible in the cytology slides. The nuclear/cytoplasmic (N/C) ratio was usually high (Papanicolaou staining; the original magnification was 400×).</p

Association of ThinPrep Bronchial Brushing Cytology with Lung Cancer Histology.

<p>Note: LC, lung cancer; SCC, squamous cell carcinoma; ADC, adenocarcinoma; SCLC, small cell lung carcinoma; SEN, sensitivity; SPE, specificity; PPV, positive predictive value; NPV, negative predictive value; MCC, Matthews correlation coefficient.</p

Cytomorphology of small cell lung carcinoma (SCLC) in ThinPrep bronchial brushing cytology.

<p>(A and B), The features of SCLC in cytology included a biphasic population of viable and degenerating tumor cells. These cells had a scant cytoplasm with a thin cyanophilic rim, single or loose clusters, molding, and DNA artifacts. The nuclear/cytoplasmic (N/C) ratio was usually high (Papanicolaou staining; the original magnification was 400×).</p

Patient Demographics.

<p>Note: A total of 595 consecutive bronchial brushing cases were included in this study with 381 male and 214 female patients.</p