Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway.

Bradykinin (BK) is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects. We previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spontaneous circulation (ROSC) after cardiac arrest. However, the precise mechanism underlying this process remains poorly understood. In this study, we treated a rat model of ROSC after cardiac arrest (induced by asphyxiation) with 150 µg/kg BK via intraperitoneal injection 48 hours after ROSC following cardiac arrest. We found that BK postconditioning effectively promoted the recovery of rat neurological function after ROSC following cardiac arrest, increased the amount of autophagosomes in the hippocampal tissue, inhibited neuronal cell apoptosis, up-regulated the expression of autophagy-related proteins LC3 and NBR1 and down-regulated p62, inhibited the expression of the brain injury marker S100ß and apoptosis-related protein caspase-3, and affected the expression of adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway-related proteins. Adenosine monophosphate-activated protein kinase inhibitor compound C clearly inhibited BK-mediated activation of autophagy in rats after ROSC following cardiac arrest, which aggravated the injury caused by ROSC. The mechanistic target of rapamycin inhibitor rapamycin enhanced the protective effects of BK by stimulating autophagy. Our findings suggest that BK postconditioning protects against injury caused by ROSC through activating the adenosine monophosphate-activated protein kinase/mechanistic target of the rapamycin pathway.

Bone marrow-derived mesenchymal stem cell transplantation attenuates overexpression of inflammatory mediators in rat brain after cardiopulmonary resuscitation.

Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation; however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline (control) or 1 × 106 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopulmonary resuscitation, possibly via regulation of inflammatory mediators. This experimental protocol was approved by the Institutional Animal Care and Use Committee of Fujian Medical University, China in January 2016 (approval No. 2016079).

Dirac potential in a rotational dissipative quantum system.

This study proposes the usage of an effective potential to investigate a dissipative quantum system with rotational velocity. After gauge transformation, a Doebner- Goldin equation (DGE) that describes the dissipative quantum system with a Dirac potential is obtained. The DGE is solved based on constraint of vertical relation between the rotational velocity field and density gradient when a harmonic oscillator model is considered. It is observed that the dissipative quantum system is directly equivalent to a monopole system and that the two gauge potentials that are given by Wu and Yang in the north and south hemispheres can be reproduced. Furthermore, a set of gauge-invariant parameters is obtained to discuss the dissipation characteristics of the system.

Time Circular Birefringence in Time-Dependent Magnetoelectric Media.

Light traveling in time-dependent media has many extraordinary properties which can be utilized to convert frequency, achieve temporal cloaking, and simulate cosmological phenomena. In this paper, we focus on time-dependent axion-type magnetoelectric (ME) media, and prove that light in these media always has two degenerate modes with opposite circular polarizations corresponding to one wave vector , and name this effect "time circular birefringence" (TCB). By interchanging the status of space and time, the pair of TCB modes can appear simultaneously via "time refraction" and "time reflection" of a linear polarized incident wave at a time interface of ME media. The superposition of the two TCB modes causes the "time Faraday effect", namely the globally unified polarization axes rotate with time. A circularly polarized Gaussian pulse traversing a time interface is also studied. If the wave-vector spectrum of a pulse mainly concentrates in the non-traveling-wave band, the pulse will be trapped with nearly fixed center while its intensity will grow rapidly. In addition, we propose an experimental scheme of using molecular fluid with external time-varying electric and magnetic fields both parallel to the direction of light to realize these phenomena in practice.

Arecoline inhibits epithelial cell viability by upregulating the apoptosis pathway: implication for oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic inflammatory disease characterized by the accumulation of excess collagen, and areca nut chewing has been proposed as a significant etiological factor for disease manifestation. However, the underlying molecular mechanisms regarding areca nut chewing-induced OSF are only partially understood. Herein, we reported that arecoline markedly induced morphologic change in HaCaT epithelial cells, but had no obvious effect on Hel fibroblast cells. MTS assay revealed that arecoline significantly suppressed HaCaT cell viability. Moreover, flow cytometric analysis indicated that arecoline substantially promoted HaCaT cell, but not Hel cell apoptosis in a dose-dependent manner. Furthermore, arecoline-induced HaCaT cell apoptosis was found to be associated with increased expression and activation of cleaved-Bid, cleaved-PARA and cleaved-caspase-3. Collectively, our results suggest that HaCaT epithelial cells are more sensitive than Hel fibroblast cells to arecoline-induced cytotoxicity, which may be involved in the pathogenesis of OSF.

Arecoline suppresses HaCaT cell proliferation through cell cycle regulatory molecules.

Betel nut chewing is the most common cause of oral submucous fibrosis (OSF). Arecoline is the main component of the betel nut, and is associated with the occurrence and development of OSF through cytotoxicity, genotoxicity and DNA damage. Similar types of stimuli elicit differential responses in different cells. In the present study, we investigated the effects of arecoline on the HaCaT epithelial and Hel fibroblast cell lines. The data showed that arecoline affected HaCaT cell morphology. MTT assay revealed that arecoline suppressed HaCaT cell proliferation. Furthermore, we found that arecoline induced the cell cycle arrest of HaCaT cells. In comparison with the untreated control cells, following treatment with ≥75 µg/ml arecoline an increased percentage of HaCaT cells remained at the G0/G1 phase of the cell cycle, accompanied by a reduced percentage of cells in the S phase. However, arecoline treatment did not significantly alter Hel cell cycle distribution. In the HaCaT epithelial cells, arecoline downregulated expression of the G1/S phase regulatory proteins cyclin D1, CDK4, CDK2, E2F1 as determined by reverse transcription-PCR analysis and western blotting. In summary, arecoline inhibits HaCaT epithelial cell proliferation and survival, in a dose-dependent manner, and cell cycle arrest in the G1/S phase, while this is not obvious in the Hel fibroblast cells. Potentially, our findings may aid in the prevention of arecoline-associated human OSF.

Therapeutic benefits of mild hypothermia in patients successfully resuscitated from cardiac arrest: A meta-analysis.

BACKGROUND: Good neurological outcome after cardiac arrest (CA) is hard to achieve for clinicians. Experimental and clinical evidence suggests that therapeutic mild hypothermia is beneficial. This study aimed to assess the effectiveness and safety of therapeutic mild hypothermia in patients successfully resuscitated from CA using a meta-analysis. METHODS: We searched the MEDLINE (1966 to April 2012), OVID (1980 to April 2012), EMBASE (1980 to April 2012), Chinese bio-medical literature & retrieval system (CBM) (1978 to April 2012), Chinese medical current contents (CMCC) (1995 to April 2012), and Chinese medical academic conference (CMAC) (1994 to April 2012). Studies were included if 1) the study design was a randomized controlled trial (RCT); 2) the study population included patients successfully resuscitated from CA, and received either standard post-resuscitation care with normothermia or mild hypothermia; 3) the study provided data on good neurologic outcome and survival to hospital discharge. Relative risk (RR) and 95% confidence interval (CI) were used to pool the effect. RESULTS: The study included four RCTs with a total of 417 patients successfully resuscitated from CA. Compared to standard post-resuscitation care with normothermia, patients in the hypothermia group were more likely to have good neurologic outcome (RR=1.43, 95% CI 1.14-1.80, P=0.002) and were more likely to survive to hospital discharge (RR=1.32, 95% CI 1.08-1.63, P=0.008). There was no significant difference in adverse events between the normothermia and hypothermia groups (P>0.05), nor heterogeneity and publication bias. CONCLUSION: Therapeutic mild hypothermia improves neurologic outcome and survival in patients successfully resuscitated from CA.

Water-filled balloon in the postoperative resection cavity improves dose distribution to target volumes in radiotherapy of maxillary sinus carcinoma.

Postoperative radiotherapy is a major treatment for patients with maxillary sinus carcinoma. However, the irregular resection cavity poses a technical difficulty for this treatment, causing uneven dose distribution to target volumes. In this study, we evaluated the dose distribution to target volumes and normal tissues in postoperative intensity-modulated radiotherapy (IMRT) after placing a water-filled balloon into the resection cavity. Three postoperative patients with advanced maxillary sinus carcinoma were selected in this trial. Water-filled balloons and supporting dental stents were fabricated according to the size of the maxillary resection cavity. Simulation CT scans were performed with or without water-filled balloons, IMRT treatment plans were established, and dose distribution to target volumes and organs at risk were evaluated. Compared to those in the treatment plan without balloons, the dose (D98) delivered to 98% of the gross tumor volume (GTV) increased by 2.1 Gy (P = 0.009), homogeneity index (HI) improved by 2.3% (P = 0.001), and target volume conformity index (TCI) of 68 Gy increased by 18.5% (P = 0.011) in the plan with balloons. Dosimetry endpoints of normal tissues around target regions in both plans were not significantly different (P > 0.05) except for the optic chiasm. In the plan without balloons, 68 Gy high-dose regions did not entirely cover target volumes in the ethmoid sinus, posteromedial wall of the maxillary sinus, or surgical margin of the hard palate. In contrast, 68 Gy high-dose regions entirely covered the GTV in the plan with balloons. These results suggest that placing a water-filled balloon in the resection cavity for postoperative IMRT of maxillary sinus carcinoma can reduce low-dose regions and markedly and simultaneously increase dose homogeneity and conformity of target volumes.

[Effect of ulinastatin on the expression of heat shock protein 70 and NF-kappaB in lung tissue in rats with paraquat poisoned].

OBJECTIVE: To observe the expression levels of heat shock protein 70 (hsp70) and NF-kappaB p65 mRNA in lung tissue of acute paraquat (PQ) poisoning rats, and intervention effects of ulinastatin (UTI). METHODS: Seventy-two Sprague-Dawley (SD) rats were randomly divided into three groups: PQ poisoning group, UTI group and control group. The rats were exposed intragastrically to PQ at the dose of 80 mg/kg to establish a model of the rat acute lung injury. The UTI group was intervened by peritoneal injection with 10000 U/kg UTI in 30 minutes. On the 12, 24, 48, 72 h after exposure, myeloperoxidase (MPO) activity in lung tissue were detected. The expression of the NF-kappaB p65 mRNA and hsp70 mRNA in lung tissue was detected by the reverse transcription-PCR (RT-PCR). The lung pathological changes of rats were observed. RESULTS: The degree of lung injury in PQ group and UTI group was higher than that in control group. But in UTI group the degree of lung injury was lower than PQ group. MPO activity in the lung tissues in PQ group was (31.72 +/- 6.42), (56.23 +/- 8.63), (87.21 +/- 10.02) and (107.21 +/- 13.52) micro/g in 12, 24, 48 and 72 h, respectively which was significantly higher than that [(11.38 +/- 1.25) micro/g] in control group (P < 0.01). MPO activity in the lung tissues in UTI group was (15.65 +/- 3.21), (35.98 +/- 5.74), (59.33 +/- 9.65) and (71.25 +/- 10.58) micro/g in 12, 24, 48 and 72 h, respectively which was significantly lower than those in PQ group (P < 0.01). The expression levels of NF-kappaB p65 mRNA of lung tissues in UTI group in 12, 24, 48 and 72 h were 0.3288 +/- 0.0147, 0.5337 +/- 0.0328, 0.7357 +/- 0.0424 and 0.7547 +/- 0.0905, respectively, which were significantly lower that those (0.4185 +/- 0.0294, 0.8532 +/- 0.0841, 0.9554 +/- 0.0975 and 1.0094 +/- 0.0703) in PQ group (P < 0.01). hsp70 mRNA expression levels in 12, 24, 48 and 72 h of the UTI group were 0.5193 +/- 0.0254, 0.8289 +/- 0.0606, 0.7566 +/- 0.0277 and 0.4873 +/- 0.0105, respectively, which were significantly higher than those (0.3897 +/- 0.0125, 0.5904 +/- 0.0186, 0.4007 +/- 0.0237 and 0.2293 +/- 0.0137) in PQ group (P < 0.01). CONCLUSION: The expression levels of hsp70 mRNA and NF-kappaB p65 mRNA of rats after intoxication increased significantly. UTI can protect the lung tissues by elevating the expression of hsp70 and reducing the expression of NF-kappaB in the lung tissues of rats with acute paraquat poisoning.

[Placement repeatability of individual oral stent used in radiotherapy of nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: Individual oral stent used in nasopharyngeal carcinoma (NPC) patients during radiotherapy can spare the oral mucosa and tongue. This study was to analyze the placement repeatability and feasibility of individual oral stent used in radiotherapy of NPC. METHODS: Individual oral stents were made for 17 naive NPC patients, and three lead markers of 2.0 mm diameter were embedded in each oral stent. The patients wearing individual oral stent were immobilized by thermoplast mask and underwent CT scan. Before and every week during radiotherapy, orthogonal (antero-posterior and lateral) X-ray films were taken in conventional simulator, respectively. Displacements of leader markers in medio-lateral (M-L),antero-posterior (A-P) and cranio-caudal (C-C) directions were respectively calculated and compared on each patient's X-ray films. At the dose of 40 Gy, a repeated CT scan was done with the same thermoplast mask and positioning markers. The displacements of co-ordinating gravity center of three lead markers and three selected bony structures between two sets of CT images for each patient were calculated and compared by ANOVA. RESULTS: A total of 240 X-ray films were taken. The displacements of lead markers were (0.69+/-0.54) mm in M-L direction, (0.49+/-0.62) mm in A-P direction, and (0.56+/-0.57) mm in C-C direction, and the overall vector displacement was (1.2+/-0.77) mm (range, 0-4.98 mm). In three-dimensional method, the displacements of co-ordinating gravity center of three lead markers were (0.75+/-0.68) mm in M-L direction, (1.25+/-1.12) mm in A-P direction, and (1.06+/-0.77) mm in C-C direction, and the overall vector displacement was (2.15+/-0.90) mm (range, 1-4.24 mm). The displacements between gravity center of three lead markers and three bony structures had no significant difference in M-L, A-P, and C-C directions (P>0.05). The overall vector displacements also had no significant difference (P=0.083). CONCLUSION: The placement repeatability of individual oral dental stent in the mouth is very good during radiotherapy of NPC, and dental stent has a fixed position relationship with bony structures.

[Sparing normal oral tissues with individual dental stent in radiotherapy for primary nasopharyngeal carcinoma patients].

BACKGROUND & OBJECTIVE: With the progression of radiotherapy techniques, the 5-year overall survival rate of nasopharyngeal carcinoma (NPC) patients has increased obviously. As the survival time prolonged, more and more attention was paid to various radiation sequelae and the quality of life of the patients. This study was to explore the role of individual dental stent in sparing normal oral tissues for primary NPC patients in radiotherapy by pushing the tongue and a part of oral mucous membrane away from the radiation fields. METHODS: Irradiation dose and volume of the tongue of a NPC patient before and after wearing dental stent was evaluated. A total of 43 patients were randomized into 2 groups: 19 in trial group and 24 in control group. Trial group wore dental stent during radiotherapy, while control group did not. Patients' weight, taste, oral mucous reaction, and tongue mucous reaction before radiotherapy and every week during radiotherapy were examined. RESULTS: Dosimetric analysis proved that the irradiation dose and volume of the tongue decreased obviously in trial group. The occurrence rate of grade 1-2 mucositis of the oral cavity was higher in trial group than in control group (73.68% vs. 62.50%), but the occurrence rate of grade 3-4 mucositis was lower in trial group than in control group (26.32% vs. 37.50%, P=0.470). By the completion of radiotherapy, 4 (21.05%) patients in trial group and 19 (79.17%) in control group suffered from taste dysfunction (P<0.001). CONCLUSION: Individual dental stent is useful in sparing the oral mucous membrane and preserving taste for primary NPC patients in radiotherapy.