Stellate ganglion block alleviates postoperative cognitive dysfunction via inhibiting TLR4/NF-κB signaling pathway.

Postoperative cognitive dysfunction (POCD) is common in aged patients after major surgery and is associated with increased risk of long-term morbidity and mortality. However, the underlying mechanism remains largely unknown and the clinical management of POCD is still controversial. Stellate ganglion block (SGB) is a clinical treatment for nerve injuries and circulatory issues. Recent evidence has identified the benefits of SGB in promoting learning and memory. We thus hypothesize that SGB could be effective in improving cognitive function after surgery. In present study, we established POCD model in aged rats via partial liver resection surgery. We found that the development of POCD was associated with the activation of toll-like receptor 4/nuclear factor kapa-B (TLR4/NF-κB) signaling pathway in the microglia in dorsal hippocampus, which induced the production of pro-inflammatory mediators (TNF-α, IL-1ß, IL-6) and promoted neuroinflammation. More importantly, we showed evidence that preoperative treatment with SGB could inhibit microglial activation, suppress TLR4/NF-κB-mediated neuroinflammation and effectively attenuate cognitive decline after the surgery. Our study suggested that SGB may serve as a novel treatment to prevent POCD in elderly patients. As SGB is safe procedure widely used in clinic, our findings can be easily translated into clinical practice and benefit more patients.

[Corrigendum] CCL22 and IL­37 inhibit the proliferation and epithelial­mesenchymal transition process of NSCLC A549 cells.

Subsequently to the publication of the above paper, the authors have drawn to our attention that, owing to errors made in the compilation of the images in Fig. 6, the images shown in Fig. 6A­C in the article were selected incorrectly (essentially, the images shown in Fig. 6A and B were alterative presentations of the same data shown in Fig. 6C). The authors were able to re­examine the original data files and retrieve the correct data panels. The revised version of Fig. 6, featuring the corrected data panels for Fig. 6A­C, is shown opposite. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 36: 2017-2024, 2016; DOI: 10.3892/or.2016.4995].

Dexmedetomidine protects intestinal ischemia-reperfusion injury via inhibiting p38 MAPK cascades.

Intestinal ischemia-reperfusion (I/R) is a life-threatening condition associated with high morbidity and mortality. Dexmedetomidine (DEX), an agonist of α2-adrenoceptor with sedation and analgesia effect, has recently been identified with protective function against I/R injury in multiple organs. However, the mechanism underlying the beneficial effect of DEX on intestine after I/R injury remained poorly understood. In the present study, using in both in vitro and in vivo models, we found that intestinal I/R injury was associated with the activation of p38 MAPK cascade, while DEX was capable of deactivating p38 MAPK and thus protect intestinal cells from apoptosis by inhibiting p38 MAPK-mediated mitochondrial depolarization and cytochrome c (Cyto C) release. Moreover, through inhibiting p38 MAPK activity, the downstream production of pro-inflammatory cytokines-regulated by NF-κB was also suppressed by DEX treatment, leading to the resolution of I/R-induced inflammation in intestine. In general, our study provided evidence that DEX protected intestine from I/R injury by inhibiting p38 MAPK-mediated mitochondrial apoptosis and inflammatory response.

A ratiometric fluorometric heparin assay based on the use of CdTe and polyethyleneimine-coated carbon quantum dots.

CdTe quantum dots (QDs) were integrated with polyethyleneimine-coated carbon dots (PEI-CDs) to form a dually emitting probe for heparin. The red fluorescence of the CdTe QDs is quenched by the PEI-CDs due to electrostatic interactions. In the presence of heparin, the blue fluorescence of PEI-CDs remains unaffected, while its quenching effect on the fluorescence of CdTe QDs is strongly reduced. A ratiometric fluorometric assay was worked out. The ratio of the fluorescences at 595 and 436 nm serves as the analytical signal. Response is linear in the concentration range of 50-600 ng·mL-1 (0.1-1.2 U·mL-1) of heparin. The limit of detection is 20 ng·mL-1 (0.04 U·mL-1). This makes the method a valuable tool for heparin monitoring during postoperative and long-term care. This assay is relatively free from the interference by other analogues which commonly co-exist with heparin in samples, and it is more robust than single-wavelength based assays. Graphical abstract In the presence of heparin, the fluorescence of polyethyleneimine-coated carbon dots (PEI-CDs) at 436 nm remains unaffected, while its quenching effect on the fluorescence of CdTe at 595 nm is strongly reduced.

Dexmedetomidine promotes the recovery of neurogenesis in aged mouse with postoperative cognitive dysfunction.

Recently, growing evidence has demonstrated Dexmedetomidine (Dex) a promising intervene preventing postoperative cognitive decline (POCD) following surgery, which is associated with neuroinflammation leading to neuronal apoptosis and deregulated neurogenesis. Previous studies suggested the anti-inflammation and anti-neuroapoptosis action of Dex. Therefore we hypothesize the promoting neurogenesis of Dex linked to stimulating BDNF and subsequent p-MPAK production in a rat model of POCD. In the present study, the POCD animal model was established by performing an exploratory laparotomy under isoflurane anaesthesia in old rats, utilizing which Dex response is confirmed by behavioural tests. Inflammatory biomarkers as IL-1ß and TNF-α, mature neuron percentage measured by doublecortin staining (DCX), promoting factors as brain derived growth factor (BDNF), phosphorylated cAMP response element binding protein (CREB) and proteins of kinase A (PKA), MAPK production as p-P38-MAPK protein express were measured. Herein, we showed that surgery reduced DCX-positive neurons and expression of BDNF representing neurogenesis profoundly. As expected, Dex rescued the associated cognitive impairment and inflammatory changes, as well as up-regulated expression of BDNF, PKA, p-CREB/CREB and following p-P38-MAPK regulation. Our results confirmed the protective Dex response and indicated the proneurogenesis role of it as well, suggesting the mechanism of beneficial effects of Dex to prevent POCD.

Effects of exogenous IL-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T cells.

BACKGROUND: This study aims to investigate the effects of exogenous interleukin (IL)-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T (Treg) cells. METHODS: After isolating the CD4+ CD25+ Treg cells from the peripheral blood, flow cytometry was used to detect the purity of the Treg cells. A549 cells were divided into blank (no transfection), empty plasmid (transfection with pIRES2-EGFP empty plasmid) or IL-37 group (transfection with pIRES2-EGFP-IL-37 plasmid). RT-PCR was used to detect mRNA expression of IL-37 and ELISA to determine IL-37 and MMP-9 expressions. Western blotting was applied to detect the protein expressions of PCNA, Ki-67, Cyclin D1, CDK4, cleaved caspase-3 and cleaved caspase-9. MTT assay, flow cytometry, scratch test and transwell assay were performed to detect cell proliferation, cycle, apoptosis, migration and invasion. Effect of exogenous IL-37 on the chemotaxis of Treg cells was measured through transwell assay. Xenograft models in nude mice were eastablished to detect the impact of IL-37 on A549 cells. RESULTS: The IL-37 group had a higher IL-37 expression, cell apoptosis in the early stage and percentage of cells in the G0/G1 phase than the blank and empty plasmid groups. The IL-37 group had a lower MMP-9 expression, optical density (OD), percentage of cells in the S and G2/M phases, migration, invasion and chemotaxis of CD4+CD25+ Foxp3+ Treg cells. The xenograft volume and weight of nude mice in the IL-37 group were lower than those in the blank and empty plasmid groups. Compared with the blank and empty plasmid groups, the IL-37 group had significantly reduced expression of PCNA, Ki-67, Cyclin D1 and CDK4 but elevated expression of cleaved caspase-3 and cleaved caspase-9. CONCLUSION: Therefore, exogenous IL-37 inhibits the proliferation, migration and invasion of human lung adenocarcinoma A549 cells as well as the chemotaxis of Treg cells while promoting the apoptosis of A549 cells.

An efficient ratiometric fluorescence sensor based on metal-organic frameworks and quantum dots for highly selective detection of 6-mercaptopurine.

The development of a simple and accurate quantitative method for the determination of 6-mercaptopurine (6-MP) is of great importance because of its serious side effects. Ratiometric fluorescence (RF) sensors are not subject to interference from environmental factors, and exhibit enhanced precision and accuracy. Therefore, a novel RF sensor for the selective detection of 6-MP was developed based on a dual-emission nanosensor. The nanosensor was fabricated by combining a blue-emission metal-organic framework (MOF) NH2-MIL-53(Al) (λem=425nm) with green-emission 3-mercaptopropionic acid-capped CdTe quantum dots (MPA-CdTe QDs) (λem=528nm) under a single excitation wavelength (335nm). Upon addition of 6-MP, the fluorescence of NH2-MIL-53(Al) in the nanohybrid was selectively quenched due to strong inner filter effects, while the fluorescence of the MPA-CdTe QDs was enhanced. The novel RF sensor exhibited higher selectivity towards 6-MP than CdTe QDs alone, and higher sensitivity than MOFs alone. 6-MP could be detected in the range of 0-50µM with a detection limit of 0.15µM (S/N=3). The developed sensor was applied for the determination of 6-MP in human urine samples and satisfactory results were obtained. Overall, a novel and efficient fluorescence-based method was developed for the detection of 6-MP in biosamples.

CCL22 and IL-37 inhibit the proliferation and epithelial-mesenchymal transition process of NSCLC A549 cells.

In the present study, we aimed to investigate the effects of CC chemokine ligand 22 (CCL22) and interleukin-37 (IL-37) on the proliferation and epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) A549 cells. pDsRed-CCL22 and pEGFP-IL-37 plasmids were constructed. A549 cells were divided into six groups: the control, the pDsRed-N1 blank plasmid, the pEGFP-C1 blank plasmid, the pDsRed-CCL22 plasmid, the pEGFP­IL-37 plasmid and the pDsRed-CCL22 + pEGFP-IL-37 plasmid group. Expression levels and localization of CCL22 and IL-37 in cells were detected by confocal microscopy. Phase-contrast microscopy was applied for observing cellular morphology. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used for detecting the mRNA levels of vimentin, N-cadherin and E-cadherin, and their protein expression levels were tested using western blotting. Constructed plasmids expressed CCL22 and IL-37, both of which had a co-localization in the cell membrane. MTT assay and cell observation results revealed that CCL22 and IL-37 inhibited the proliferation and EMT process of the A549 cells. The results of RT-qPCR and western blotting revealed that decreased vimentin and N-cadherin mRNA and protein expression levels, and increased E-cadherin mRNA and protein expression levels were found in the pDsRed-CCL22 plasmid, pEGFP-IL-37 plasmid and pDsRed­CCL22 + pEGFP­IL-37 plasmid groups when compared with the control, the pDsRed-N1 blank plasmid and the pEGFP-C1 blank plasmid groups (all P<0.05), and decreased vimentin and N-cadherin mRNA and protein expression levels and increased E-cadherin mRNA and protein expression levels were found in the pDsRed­CCL22 + pEGFP­IL-37 plasmid group when compared with the pDsRed-CCL22 plasmid and the pEGFP­IL-37 plasmid groups (all P<0.05). CCL22 and IL-37 with a co-localization in the A549 cells inhibited the proliferation and EMT process in A549 cells. The antitumor effects of CCL22 and IL37 provide a strategy for the treatment of NSCLC.