Bisdemethoxycurcumin Inhibits VEGF-Induced HUVECs Proliferation, Migration and Invasion through AMPK/mTOR Pathway-Dependent Autophagy Activation and Cell Cycle Arrest.

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis, which plays a key role in the proliferation, migration and invasion of endothelial cell. Bisdemethoxycurcumin (BDMC) is a natural demethoxy curcumin derivative. In this study, we explored the mechanisms whereby BDMC is able to influence the proliferative, migratory and invasive activity of human umbilical vein endothelial cells (HUVECs) in response to VEGF treatment. These experiments revealed that BDMC at 10 and 20 µM suppressed HUVECs proliferation in response to VEGF (10 ng/mL) without impacting the proliferation in absence of VEGF. BDMC treatment also signifantly suppressed VEGF-induced migratory and invasive activity in HUVECs. However, the selective AMP-activated protein kinase (AMPK) inhibitor compound C (3 µM) treatment signifantly reversed all of these effects. Flow cytometric assay showed BDMC treatment was found to induce G0/G1 phase cell cycle arrest. Western blotting further indicated that BDMC treatment increased the ratios of p-AMPK/AMPK and LC3B/LC3A, up-regulated the expression of Beclin-1, decreased the ratio of p-mammalian target of rapamycin (mTOR)/mTOR, down-regulated the expression of cyclin D1 and CDK4. Overall, these data suggested that BDMC may exert benefical effect on HUVECs activation by activating autophagy and inducing cell cycle arrest through regulation of the AMPK/mTOR pathway, which could provide a potential compound candidate for the treatment of diseases related to VEGF overproduction.

Feasibility and safety of computed tomography-guided intrapulmonary injection of indocyanine green for localization of peripheral pulmonary ground-glass nodules.

Background: The early surgical intervention for pulmonary ground-glass nodules (GGNs) has become increasingly important, but accurate identification of these nodules during thoracoscopic surgery poses challenges due to the need for sublobar resections and reliance on visual and tactile perception alone. The prognosis of the procedure is closely tied to the use of precise positioning technology. Thus, it is crucial to develop an accurate positioning technology that can improve patient prognosis. Methods: Clinical data from the cardiothoracic department of a tertiary hospital in Shanghai were collected and analyzed between January 2020 and December 2021. The patients were categorized into 2 groups: an indocyanine green (ICG) group and a hook-wire group. Outcome measures including success rate, complications, procedure time, localization-related pain, and interval time were assessed. Adverse events and reactions were reported and compared between the 2 groups. Results: A total of 62 patients (17 males and 45 females, aged 50.5±13.2 years) were in the ICG group, while 66 patients (23 males and 43 females, aged 48.4±12.9 years) were localized in the hook-wire group. The success rate was comparable between the 2 groups. However, the ICG group showed significant advantages over the hook-wire group in terms of procedure time (22.6±4.4 vs. 24.1±4.9 min; P=0.012), localization-related pain (P<0.001), and interval time [median and interquartile range (IQR): 3 (0.7, 104.9) vs. 1.2 (0.5, 3.3) h; P<0.001]. In the ICG group, there were 11 cases of pneumothorax, 4 cases of hemothorax, and 2 cases of ICG diffusion. In the hook-wire group, there were 24 cases of pneumothorax, 25 cases of hemothorax, and 2 cases of dislodgement. The ICG group had fewer complications, including pneumothorax (P=0.018) and hemothorax (P=0.007), compared to the hook-wire group. Conclusions: Computed tomography (CT)-guided intrapulmonary injection of ICG for preoperative localization of peripheral pulmonary GGNs is a practical and safe technique. It offers advantages in terms of reduced procedure time, localization-related pain, and interval time compared to the hook-wire method. Moreover, the ICG technique results in fewer complications, making it a valuable preoperative localization technique worthy of popularization.

Panoramic quality assessment tool for investigator initiated trials.

Objectives: Quality can be a challenge for Investigator initiated trials (IITs) since these trials are scarcely overseen by a sponsor or monitoring team. Therefore, quality assessment for departments managing clinical research grants program is important and urgently needed. Our study aims at developing a handy quality assessment tool for IITs that can be applied by both departments and project teams. Methods: The framework of the quality assessment tool was developed based on the literature studies, accepted guidelines and the Delphi method. A total of 272 ongoing IITs funded by Shanghai non-profit organizations in 2015 and 2016 were used to extract quality indexes. Confirmatory factor analysis (CFA) was used to further evaluate the validity and feasibility of the conceptual quality assessment tool. Results: The tool consisted of 4 critical quality attributes, including progress, quality, regulation, scientificity, and 13 observed quality indexes. A total of 257 IITs were included in the validity and feasibility assessment. The majority (60.29%) were Randomized Controlled Trial (RCT), and 41.18% were multi-center studies. In order to test the validity and feasibility of IITs quality assessment tool, CFA showed that the model fit the data adequately. (CMIN/DF = 1.868, GFI = 0.916; CFI = 0.936; TLI = 0.919; RMSEA = 0.063; SRMR = 0.076). Different types of clinical studies fit well in the tool. However, RCT scored lower than prospective cohort and retrospective study in enrollment progress (7.02 vs. 7.43, 9.63, respectively). Conclusion: This study established a panoramic quality assessment tool based on the Delphi method and CFA, and the feasibility and effectiveness of the tool were verified through clinical research examples. The use of this tool can help project management departments effectively and dynamically manage research projects, rationally allocate resources, and ensure the quality of IITs.

Human placenta mesenchymal stem cells suppress airway inflammation in asthmatic rats by modulating Notch signaling.

Neurogenic locus notch homolog protein (Notch) signaling mediates intracellular communication and may regulate cell fate decisions, including cell proliferation, differentiation, and apoptosis. Mesenchymal stem cells (MSCs) possess immunomodulatory properties and the potential for use in stem cell replacement treatments. The aim of the present study was to evaluate the therapeutic effects of human placenta­deviated MSCs (hPMSCs) in asthma and to investigate the mechanisms of Notch signaling mediated by transplanted MSCs. A Sprague­Dawley rat ovalbumin (OVA)­sensitized acute asthma model was established and challenged. MSCs derived from human placenta (hPMSCs) were transplanted into the asthmatic rats. Transplantation resulted in reduced Notch­1, Notch­2 and jagged­1, and increased Notch­3, Notch­4 and delta­like ligand (delta)­4 expression in lung, blood, and lymph samples. Notch­1, Notch­2, and jagged­1 expression in OVA­treated rats was significantly decreased compared with controls and hPMSC­treated rats; however, Notch­3, Notch­4 and delta­4 expression was significantly increased. Serum interferon­Î³ significantly increased after hPMSCs transplantation, whereas interleukin­4 and immunoglobulin E decreased. In OVA­treated rats, Notch­1, Notch­2 and jagged­1 levels were increased in the lymph compared with the blood, although Notch­4 and delta­4 levels were decreased. Peribronchial infiltration of cells and goblet cell hyperplasia were markedly decreased in the OVA + hPMSCs group compared with those in the OVA­treated and control groups. Alterations in Notch signaling pathway expression were accompanied by decreased inflammatory cell infiltration, goblet cell hyperplasia and mucus production in lung tissues. The results of the present study are consistent with hPMSC suppression of asthma symptoms and inflammation by regulating the Notch signaling pathway in the rat asthma model.

Determination of 2-methoxyestradiol by chemiluminescence based on luminol-KMnO4-CdTe quantum dots system.

In this study, water-soluble CdTe quantum-dots (QDs) capped with glutathione (GSH) was synthesized. It was found that CdTe QDs could greatly enhance the chemiluminescence (CL) emission from the luminol-KMnO4 system in alkaline medium, and 4 nm CdTe QDs was used as catalysts to enhance the reaction sensitivity. The CL intensity of CdTe QDs-luminol-KMnO4 was strongly inhibited in the presence of 2-methoxyestradiol (2-ME) and the relative CL intensity was in linear correlation with the concentration of 2-ME. Based on this inhibition, a novel CL method with a lower detection limit and wider linear range was developed for the determination of 2-ME. The detection limit of plasma samples was 3.07×10(-10) g mL(-1) with a relative standard deviation of 0.24% for 8.0×10(-9) g mL(-1) 2-ME. The method was successfully applied for determination of 2-ME in plasma samples. The possible CL reaction mechanism was also discussed briefly.

A novel restricted access material combined to molecularly imprinted polymers for selective solid-phase extraction and high performance liquid chromatography determination of 2-methoxyestradiol in plasma samples.

A feasibility study was performed in order to ensure the possibilities in using a restricted access material combined to molecularly imprinted polymers (RAM-MIP) as sorbent material in solid phase extraction (SPE) for clean-up of 2-methoxyestradiol (2-ME) from plasma samples. The MIP with hydrophilic external layer was designed by precipitation polymerization. The polymer was characterized by thermogravimetric analysis (TGA) and scanning electron microscope (SEM). The use of analogs of 2-ME as templates, in combination with a chromatographic separation of the analytes in the sample, overcame the problem of the template bleeding. To demonstrate the property of the RAM-MIP obtained, a comparison of commercially available C18 SPE was performed. The results showed that the RAM-MISPE recoveries were significantly higher than that of C18 SPE for 2-ME in trace concentration. During the extraction process, 2-ME was sufficiently cleaned for further chromatographic analysis with no interferences from template leakage and matrix. Good linearity was obtained from 0.06 to 20 µg mL(-1) with the correlation coefficient r>0.9991. The coefficient of variation of the inter-assay precision was less than 11.9%. The recoveries of 2-ME in rat plasma at three spiked levels were in the range of 99.10-101.00%. Based on the analytical validation results, the proposed method (RAM-MIP off-line SPE/HPLC) can be a useful tool to determine 2-ME in rat plasma samples.