Increased infiltration of M2-polarized tumour-associated macrophages is highly associated with advanced disease stage and high expression of PD-L1 in buccal mucosa carcinoma.

OBJECTIVE: To assess the infiltration characteristics of tumour-associated macrophages (TAMs) in buccal mucosa carcinoma (BMC) and the correlation of these features with clinicopathological factors. MATERIALS AND METHODS: Immunohistochemistry was used to detect the expression of TAM-related markers (CD68, CD163, CD206), CD8+ T cell markers, PD-L1, and epidermal growth factor receptor (EGFR) in 46 patients with mucosal cancer after radical surgery. In addition, the correlation between TAM infiltration and clinical characteristics, PD-L1 expression, and EGFR expression was analysed. RESULTS: A high infiltration level of M2-polarized (CD206+) TAMs and M2-polarized (CD163+) TAMs was more common in stage T3-T4, N+, III-IV patients than in other patient groups (P < 0.05). The infiltration degree of M2-polarized (CD68+) TAMs was positively correlated with the PD-L1 TPS (P = 0.0331). The infiltration level of M2-polarized (CD206+) TAMs was higher in the EGFR high expression group than in the EGFR low expression group (P = 0.040). CONCLUSION: High infiltration of M2-polarized TAMs is highly associated with advanced disease stage and higher expression of PD-L1 and EGFR in BMCs, suggesting that M2-polarized TAMs infiltration can serve as a potential therapeutic target.

Health risk assessment of heavy metals and disinfection by-products in drinking water in megacities in China: A study based on age groups and Monte Carlo simulations.

Heavy metal(loid)s (HMs) and disinfection by-products (DBPs) in drinking water pose risks to human health and jeopardize drinking water. Water-related behaviors vary significantly among different age groups and regions. In this study, the carcinogenic and non-carcinogenic risks of HMs (As, Cd, Cr6+, Cu, Pb, and Zn) and DBPs (bromodichloromethane (BDCM), bromoform, chloroform, dibromochloromethane (DBCM), dichloroacetic acid (DCAA), and trichloroacetic acid (TCAA)) in drinking water in two Chinese megacities (Beijing in North China and Guangzhou in South China) via multiple exposure pathways were assessed. The results showed that children aged 9 months to 2 years had a total carcinogenic risk (TCR) and hazard index (HI) above acceptable levels, indicating that despite the drinking water quality in the selected megacities meeting the current Chinese national standards (GB 5749-2022), the health risks of exposure to HMs and DBPs in drinking water for local young children should not be neglected. Specifically, the carcinogenic risk (CR) of exposure to As in drinking water for children < 18-years-old, who were divided into different age groups, was 1.5-2.0- and 4.5-5.9-times higher than the TCR of exposure to DBPs in Beijing and Guangzhou, respectively. Regarding children aged 9 months to 2 years, the exposure to TCAA accounted for the largest proportion (35.6 %) of the TCR of exposure to DBPs in Beijing drinking water, 5.4-times higher than that in Guangzhou; whereas, the TCR of exposure to DBPs in Guangzhou drinking water was predominantly caused by exposure to chloroform, accounting for 40.6 % of the TCR and 1.5-times higher than that in Beijing. In addition, the CR of exposure to DCAA in drinking water in both megacities accounted for a large proportion of the TCR for children aged 9 months to 2 years. Monte Carlo simulations showed that 62.2 % and 42.6 % of the TCR of simultaneous exposure to As and DBPs in drinking water exceeded the acceptable level for sensitive populations, that is, children aged 1-2 years in Beijing (95th percentile = 4.2 × 10-4) and children aged 9-12 months in Guangzhou (95th percentile = 5.2 × 10-4), respectively. This elaborate health risk assessment sheds light on improving the water quality indices to guarantee drinking water safety in China.

Soil microbial responses to simultaneous contamination of antimony and arsenic in the surrounding area of an abandoned antimony smelter in Southwest China.

Soil contamination with heavy metal(loid)s may influence microbial activities in the soil, and consequently jeopardize soil health. Microbial responses to soil contamination play an important role in ecological risk assessment. This study investigated the effect of heavy metal(loid)s contamination on microbial community structure and abundance in the surrounding soil of an abandoned antimony (Sb) smelter in Qinglong county, Guizhou province, Southwest China. A total of 46 soil samples were collected from ten sampling sites (labelled as A-I, and CK) across the study area at depths of 0-2, 2-10, 10-20, 20-30, 30-40, and 40-50 cm. The soil samples were analyzed for total and bioavailable heavy metal(loid) concentrations, bacterial, fungal, and archaeal community structures, diversities, and functions, together with soil basic physicochemical properties. Much greater ecological risk of Sb and arsenic (As) was present in the surface soil (0-2 cm) compared to that in the subsoils. The activities of dominant microorganisms tended to be associated with soil pH and heavy metal(loid)s (i.e., Sb, As, lead (Pb), cadmium (Cd), and chromium (Cr)). Bacteria associated with IMCC26256, Rhizobiales, Burkholderiales, and Gaiellales, and archaea associated with Methanocellales were estimated to be tolerant to high concentrations of Sb and As in the soil. In addition, the magnitude of soil microbial responses to Sb and As contamination was in the order of archaea > bacteria > fungi. In contrast to the negligible response of fungi and negative response of bacteria to Sb and As contamination, there was a strongly positive correlation between archaeal activity and total Sb and As concentrations in the soil. Our findings provide a theoretical basis for the remediation of Sb smelter-affected soil.

Security risk assessment and visualization study of key nodes of sea lanes: case studies on the Tsugaru Strait and the Makassar Strait.

Key nodes of sea lanes are important hubs for global trade and cargo transportation and play important roles in ensuring the safety of maritime transportation and maintaining the stability of the global supply chain. The safety guarantee of key nodes of sea lanes is facing more risks and higher requirements currently because the global shipping industry is gradually recovering. This paper focuses on key nodes of sea lanes, conducting regional security risk assessment and risk spatial scale visualization. A set of security risk assessment and visualization study methods for key nodes of sea lanes is constructed, which includes constructing a security risk assessment index system of key nodes of sea lanes with 25 indicators selected from three risk categories (hazard, vulnerability and exposure, and mitigation capacity) and using geospatial analysis to form the multi-criteria spatial mapping layers and then creating comprehensive risk layers to realize the risk visualization in the strait area by weighted overlaying based on the combined weights calculated by Analytic Hierarchy Process and Grey Relational Analysis. After taking the Tsugaru Strait and Makassar Strait as case studies, the results show that the comprehensive risk layers can effectively present the spatial distribution of security risks of key nodes of sea lanes, reflecting the spatial changes of risk levels (i.e., very low, low, medium, high and very high) and the methods can precisely identify and analyze crucial factors affecting the security risk of key nodes. These findings may strengthen the risk prevention and improve the safety of the navigation environment in the strait to ensure the safety and stability of maritime trade.

Sensitization of Non-Small Cell Lung Cancer Cells to Gefitinib and Reversal of Epithelial-Mesenchymal Transition by Aloe-Emodin Via PI3K/Akt/TWIS1 Signal Blockage.

Objective: To explore the impacts of AE (aloe-emodin) in gefitinib-resistant NSCLC (non-small cell lung cancer) cells and the corresponding mechanism. Methods: PC9 and PC9-GR cells were cultured and treated by gefitinib, AE, or the combination of the two drugs. Then, viability, apoptosis, migration and invasion of cells were investigated using CCK-8, TUNEL, wound healing assay, and transwell assay, respectively. Female BALB/c nude mice were employed for the establishment of xenograft tumor models to examine the role of AE in tumor growth. Results: PC9-GR cells showed reduced apoptosis and enhanced cell viability, migration and invasion upon treatment by gefitinib, compared with PC9 cells. E-cahherin in PC9-GR cells was down-regulated, while Vimentin, Snail2 (or Slug) and Twist1 in PC9-GR cells were up-regulated, compared with PC9 cells. Meanwhile, treatment by a combination of gefitinib and AE significantly strengthened apoptosis of PC9-GR cells, while attenuated their migration and invasion, compared with the control group or treatment by gefitinib or AE alone. WB results showed that AE could reverse EMT and activation of PI3K/AKT signalling pathway in PC9-GR cells. In vivo experiments showed that tumor growth and EMT of PC9-GR cells were dramatically repressed after treatment by a combination of AE and gefitinib. Additionally, the use of SC97 (a PI3K/Akt pathway activator) could counteract the effects of AE in gefitinib-resistant PC9 cells. Conclusions: AE could enhance the gefitinib sensitivity of PC9-GR cells and reverse EMT by blocking PI3K/Akt/TWIS1 signal pathway.

Comprehensive evaluation of environmental dimension reduction of multi-type islands: a sustainable development perspective.

In recent years, the sustainable development of islands has attracted increasing attention from countries all over the world. An important prerequisite for promoting sustainable development is to understand the foundation and sustainable development potential of islands. Constructing index systems and models is an important means of evaluating the sustainability of islands. This study used factor analysis (FA) to construct an indicator system and set weights. Thirty-eight indicators were set from both natural and social directions to evaluate the sustainable development of seven typical islands in China. The FA removed the 10 indicators that were too relevant, and the 28 effective indicators were reduced into 9 main factors for evaluation. The results showed that the evaluation results are in line with the actual development of the island, which verifies the applicability of the model to different types of islands. The study also found that the changing trends of island social sustainability, tourism sustainability, ecological sustainability, resource sustainability, and economic sustainability are consistent. The value of fully balanced islands is higher than that of unbalanced or undeveloped islands. Among the seven islands, social islands have the highest total value, and ecological islands have the lowest total value.

Antifungal activity of thymol and carvacrol against postharvest pathogens Botrytis cinerea.

Botrytis cinerea is a primary pathogen causing stem and fruit rot during pre- and post-harvest. In the present study, the main purpose was to inquire into the antifungal activity and potential mechanisms of thymol and carvacrol against B. cinerea. During the experiment, the effects of thymol and carvacrol on physical and biochemical parameters of B. cinerea were evaluated. Results indicated that thymol and carvacrol exhibited strong antifungal activity against the targeted pathogen, with minimum inhibitory concentration and minimum fungicidal concentration of 65 mg/L and 100 mg/L for thymol, and 120 µL/L and 140 µL/L for carvacrol. Thymol and carvacrol changed obviously the morphology of B. cinerea hyphae by disrupting and distorting the mycelia through scanning electron microscopy. The membrane permeability of B. cinerea hyphae was prompted with the increment of two chemical agents' concentration, as evidenced by extracellular conductivity increase, the release of cell constituent, and the decrease of extracellular pH. Furthermore, a marked decline in total lipid content of B. cinerea cells was induced by the two chemical agents, suggesting that the cell membrane structures were destructed. Therefore, present results indicated that thymol and carvacrol may be used as a good alternative to conventional fungicides against B. cinerea in controlling grey molds in horticultural products.

Transcription profile analysis of Lycopersicum esculentum leaves, unravels volatile emissions and gene expression under salinity stress.

Salinity stress can impede development and plant growth adversely. However, there is very little molecular information on NaCl resistance and volatile emissions in Lycopersicum esculentum. In order to investigate the effects of salt stress on the release of volatile compounds, we quantified and compared transcriptome changes by RNA-Seq analysis and volatile constituents with gas chromatography/mass spectrometry (GC/MS) coupled with solid-phase microextraction (SPME) after exposure to continuous salt stress. Chemical analysis by GC-MS analysis revealed that NaCl stress had changed species and quantity of volatile compounds released. In this research, 21,578 unigenes that represented 44,714 assembled unique transcripts were separated from tomato leaves exposed to NaCl stress based on de novo transcriptome assembly. The total number of differentially expressed genes was 7210 after exposure to NaCl, including 6200 down-regulated and 1208 up-regulated genes. Among these differentially expressed genes (DEGs), there were eighteen differentially expressed genes associated with volatile biosynthesis. Of the unigenes, 3454 were mapped to 131 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, mainly those are involved in RNA transport, plant-pathogen interactions, and plant hormone signal transduction. qRT-PCR analysis showed that NaCl exposure affected the expression profiles of the biosynthesis genes for eight volatile compounds (IPI, GPS, and TPS, etc.), which corresponded well with the RNA-Seq analysis and GC-MS results. Our results suggest that NaCl stress affects the emission of volatile substances from L. esculentum leaves by regulating the expression of genes that are involved in volatile organic compounds' biosynthesis.

Anti-fungal activity, mechanism studies on α-Phellandrene and Nonanal against Penicillium cyclopium.

BACKGROUND: Essential oils from plants have been reported to have wide spread antimicrobial activity against various bacterial and fungal pathogens, and these include α-Phellandrene, Nonanal and other volatile substances. However, biological activities of α-Phellandrene and Nonanal have been reported only in a few publications. Further investigations are necessary to determine the antimicrobial activity of these compounds, especially for individual application, to establish the possible mechanism of action of the most active compound. RESULTS: The results are shown that α-Phellandrene and Nonanal have a dose-dependent inhibition on the mycelial growth of Penicillium cyclopium. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) are 1.7 and 1.8 mL/L for α-Phellandrene, 0.3 and 0.4 mL/L for Nonanal, respectively. The volatile compounds altered the morphology of P. cyclopium hyphae by causing loss of cytoplasmic material and distortion of the mycelia. The membrane permeability of P. cyclopium increased with increasing concentrations of the two volatile compounds, as evidenced by cell constituent release, extracellular conductivity and induced efflux of K+. Moreover, the two volatile compounds induced a decrease in pH and in the total lipid content of P. cyclopium, which suggested that cell membrane integrity had been compromised. CONCLUSIONS: The results demonstrated that α-Phellandrene and Nonanal could significantly inhibit the mycelia growth of P. cyclopium by severely disrupting the integrity of the fungal cell membrane, leading to the leakage of cell constituents and potassium ions, and triggering an increase of the total lipid content, extracellular pH and membrane permeability. Our present study suggests that α-Phellandrene and Nonanal might be a biological fungicide for the control of P. cyclopium in postharvest tomato fruits.

Electroacupuncture preconditioning-induced neuroprotection may be mediated by glutamate transporter type 2.

Electroacupuncture has been shown to induce a preconditioning effect in the brain. The mechanisms for this protection are not fully elucidated. We hypothesize that this protection is mediated by excitatory amino acid transporters (EAATs) that have been shown to be neuroprotective. To test this hypothesis, two-month old male Sprague-Dawley rats and EAAT type 3 (EAAT3) knockout mice received or did not receive 30-min electroacupuncture once a day for five consecutive days. They were subjected to a 120-min middle cerebral arterial occlusion (MCAO) at 24h after the last electroacupuncture. Neurological outcome was assessed 2days after the MCAO. Brain tissues were harvested at 24h after the last electroacupuncture for Western blotting. Rats subjected to electroacupuncture at the Baihui acupoint had smaller brain infarct volumes and better neurological deficit scores than control rats. Electroacupuncture increased EAAT type 2 (EAAT2) in the cerebral cortex, tended to increase EAAT3 in the hippocampus, and had no effect on EAAT type 1 expression. Dihydrokainate, an EAAT2 inhibitor, worsened the neurological outcome of rats with electroacupuncture pretreatment. Electroacupuncture pretreatment at the Baihui acupoint increased EAAT2 in the cerebral cortex and improved the neurological outcome of EAAT3 knockout mice. Together, our results suggest that EAAT2 may mediate the electroacupuncture preconditioning-induced neuroprotection.

Carboxy terminus of heat shock protein (HSP) 70-interacting protein (CHIP) inhibits HSP70 in the heart

Heat shock protein (HSP) 70 plays a critical role in protecting the heart from various stressor-induced cell injuries; the mechanism remains to be further understood. The present study aims to elucidate the effect of a probiotics-derived protein, LGG-derived protein p75 (LGP), in alleviating the ischemia/reperfusion (I/R)-induced heart injury. We treated rats with the I/R with or without preadministration with LGP. The levels of HSP70 and carboxy terminus of HSP70-interacting protein (CHIP) in the heart tissue were assessed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of CHIP on suppression of HSP70 and the effect of LGP on suppression of CHIP were investigated with an I/R rat model and a cell culture model. The results showed that I/R-induced infarction in the heart could be alleviated by pretreatment with LGP. HSP70 was detected in naïve rat heart tissue extracts. I/R treatment significantly suppressed the level of HSP70 and increased the levels of CHIP in the heart. A complex of CHIP/HSP70 was detected in heart tissue extracts. The addition of recombinant CHIP to culture inhibited HSP70 in heart cells. LGP was bound CHIP in heart cells and prevented the CHIP from binding HSP70. In summary, I/R can suppress HSP70 and increase CHIP in heart cells. CHIP can suppress HSP70 that can be prevented by pretreatment with LGP. The results imply that CHIP may be a potential target in the prevention of I/R-induced heart cell injury (AU)

Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

BACKGROUND: Electroacupuncture (EA) pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. RESULTS: EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. CONCLUSIONS: EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

Anesthesia with sevoflurane and remifentanil under spontaneous respiration assisted with high-frequency jet ventilation for tracheobronchial foreign body removal in 586 children.

BACKGROUND: Foreign body aspiration is a common life-threatening event in young children. Tracheobronchial foreign body removal is usually performed by rigid tracheobronchoscopy under general anesthesia. Anesthetic and ventilation techniques vary greatly among anesthesiologists and institutions. In the present retrospective study, we report our anesthetic experience over 5 years. We describe complications and outcomes and analyze the clinical characteristics of anesthesia and ventilation. METHODS: We retrospectively reviewed relevant clinical findings of 586 pediatric patients treated with rigid tracheobronchoscopy under general anesthesia. All procedures were performed under inhaled sevoflurane anesthesia combined with remifentanil infusion, with spontaneous respiration assisted by high-frequency jet ventilation (HFJV) and topical airway anesthesia. RESULTS: Among 586 patients, the foreign body was successfully removed by rigid tracheobronchoscopy in 558 patients, and no foreign body was found in 28 patients. Laryngospasm was observed during the procedure in five patients. Hypoxemia was observed in 15 patients (2.6%). No severe complications or deaths occurred. The mean operation time was 22 min and the average hospital stay was 2 days. CONCLUSION: Inhaled sevoflurane anesthesia combined with remifentanil infusion, with spontaneous respiration assisted by HFJV and topical airway anesthesia, is safe and effective for tracheobronchial foreign body removal.

Noninvasive limb remote ischemic preconditioning contributes neuroprotective effects via activation of adenosine A1 receptor and redox status after transient focal cerebral ischemia in rats.

PURPOSES: To investigate whether activation of adenosine A1 receptor (A1R) through limb remote ischemic preconditioning (RIPC) by a noninvasive tourniquet contribute neuroprotective effects against rat focal cerebral ischemic injury induced by transient middle cerebral artery occlusion (MCAO). METHODS: One hundred twenty-eight Sprague-Dawley (SD) rats were randomly assigned into eight groups (n=16 each): MCAO, Control, 8-cyclopentyl-1,3-dipropulxanthine (DPCPX, Adenosine A1 receptor antagonist), RIPC, DPCPX+RIPC, Vehicle+RIPC, 2-chloro-N(6)-cyclopentyladenosine (CCPA, Adenosine A1 receptor agonist) and CCPA+DPCPX groups. All animals underwent right middle cerebral artery occlusion (MCAO) for 2 h. Limb RIPC consisted of three cycles of 5-minute ischemia followed by 5-minute reperfusion in right hind-limb by tourniquet application. Neurological deficit scores were evaluated 24 h after reperfusion, and then the infarct volume was assessed with diffusion weighted imaging (DWI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. Inflammation was assessed by serum tumor necrosis factor α (TNF(α)) and NO; oxidative stress was estimated by malondialdehyde (MDA) and 4-hydroxyalkenals (4-HAD), superoxide dismutase (SOD) activity and GSH. RESULTS: Animals in the RIPC, Vehicle+RIPC and CCPA groups developed lower neurological deficit scores and smaller brain infarct volumes than the Control group (P<0.01). Animals in the DPCPX, DPCPX+RIPC and CCPA+DPCPX groups developed higher neurological deficit scores and larger brain infarct volumes than the RIPC, Vehicle+RIPC and CCPA groups (P<0.01). DPCPX abolished the protective effects of RIPC and CCPA. RIPC or CCPA induced a significant increase in brain MnSOD (manganese SOD) activity and NO generation, and this activity was abolished by DPCPX pretreatment. RIPC or CCPA induced a significant reduction (P<0.05) in the GSH and MDA+4HDA concentration and an accumulation in the GSSG concentration in both compartments (serum and tissue) as compared with the MCAO group. CONCLUSIONS: The present study demonstrates that limb RIPC induced by noninvasive tourniquet reduces cerebral ischemic injury in rats, and the effect of neuroprotection may depend on the activation of adenosine A1 receptors. CCPA pretreatment can induce delayed ischemic tolerance against cerebral ischemia/reperfusion injury. These protective effects are associated with a reduction in oxidative stress, inflammation and endogenous antioxidant preservation.

Carboxy terminus of heat shock protein (HSP) 70-interacting protein (CHIP) inhibits HSP70 in the heart.

Heat shock protein (HSP) 70 plays a critical role in protecting the heart from various stressor-induced cell injuries; the mechanism remains to be further understood. The present study aims to elucidate the effect of a probiotics-derived protein, LGG-derived protein p75 (LGP), in alleviating the ischemia/reperfusion (I/R)-induced heart injury. We treated rats with the I/R with or without preadministration with LGP. The levels of HSP70 and carboxy terminus of HSP70-interacting protein (CHIP) in the heart tissue were assessed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of CHIP on suppression of HSP70 and the effect of LGP on suppression of CHIP were investigated with an I/R rat model and a cell culture model. The results showed that I/R-induced infarction in the heart could be alleviated by pretreatment with LGP. HSP70 was detected in naïve rat heart tissue extracts. I/R treatment significantly suppressed the level of HSP70 and increased the levels of CHIP in the heart. A complex of CHIP/HSP70 was detected in heart tissue extracts. The addition of recombinant CHIP to culture inhibited HSP70 in heart cells. LGP was bound CHIP in heart cells and prevented the CHIP from binding HSP70. In summary, I/R can suppress HSP70 and increase CHIP in heart cells. CHIP can suppress HSP70 that can be prevented by pretreatment with LGP. The results imply that CHIP may be a potential target in the prevention of I/R-induced heart cell injury.

Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats.

BACKGROUND: We have previously reported that electroacupuncture (EA) pretreatment induced tolerance against cerebral ischemic injury, but the mechanisms underlying this effect of EA are unknown. In this study, we assessed the effect of EA pretreatment on the expression of α7 nicotinic acetylcholine receptors (α7nAChR), using the ischemia-reperfusion model of focal cerebral ischemia in rats. Further, we investigated the role of high mobility group box 1 (HMGB1) in neuroprotection mediated by the α7nAChR and EA. METHODS: Rats were treated with EA at the acupoint "Baihui (GV 20)" 24 h before focal cerebral ischemia which was induced for 120 min by middle cerebral artery occlusion. Neurobehavioral scores, infarction volumes, neuronal apoptosis, and HMGB1 levels were evaluated after reperfusion. The α7nAChR agonist PHA-543613 and the antagonist α-bungarotoxin (α-BGT) were used to investigate the role of the α7nAChR in mediating neuroprotective effects. The roles of the α7nAChR and HMGB1 release in neuroprotection were further tested in neuronal cultures exposed to oxygen and glucose deprivation (OGD). RESULTS: Our results showed that the expression of α7nAChR was significantly decreased after reperfusion. EA pretreatment prevented the reduction in neuronal expression of α7nAChR after reperfusion in the ischemic penumbra. Pretreatment with PHA-543613 afforded neuroprotective effects against ischemic damage. Moreover, EA pretreatment reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis and HMGB1 release following reperfusion, and the beneficial effects were attenuated by α-BGT. The HMGB1 levels in plasma and the penumbral brain tissue were correlated with the number of apoptotic neurons in the ischemic penumbra. Furthermore, OGD in cultured neurons triggered HMGB1 release into the culture medium, and this effect was efficiently suppressed by PHA-543,613. Pretreatment with α-BGT reversed the inhibitory effect of PHA-543,613 on HMGB1 release. CONCLUSION: These data demonstrate that EA pretreatment strongly protects the brain against transient cerebral ischemic injury, and inhibits HMGB1 release through α7nAChR activation in rats. These findings suggest the novel potential for stroke interventions harnessing the anti-inflammatory effects of α7nAChR activation, through acupuncture or pharmacological strategies.

Preconditioning with repeated hyperbaric oxygen induces myocardial and cerebral protection in patients undergoing coronary artery bypass graft surgery: a prospective, randomized, controlled clinical trial.

OBJECTIVES: To evaluate the cerebral and myocardial protective effects of hyperbaric oxygen preconditioning in both on-pump and off-pump coronary artery bypass graft surgery. DESIGN: A prospective, randomized, single-blinded study including patients scheduled for elective on-pump or off-pump surgery between December 2007 and February 2009. SETTING: A tertiary care university teaching hospital. PARTICIPANTS: Forty-nine elective on-pump or off-pump coronary artery bypass graft surgery patients. INTERVENTIONS: Patients were randomized to either the control (15 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) or hyperbaric oxygen (HBO; 14 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) groups. Patients in the HBO groups underwent preconditioning for 5 days before surgery. MEASUREMENTS AND MAIN RESULTS: On-pump coronary artery bypass graft surgery patients preconditioned with HBO had significant decreases in S100B protein, neuron-specific enolase, and troponin I perioperative serum levels compared with the on-pump control group. Postsurgically, patients in the on-pump HBO group had a reduced length of stay in the intensive care unit and a decreased use of inotropic drugs. Serum catalase activity 24 hours postoperatively was significantly increased compared with the on-pump control group. In the off-pump groups, there was no difference in any of the same parameters. CONCLUSIONS: Preconditioning with HBO resulted in both cerebral and cardiac protective effects as determined by biochemical markers of neuronal and myocardial injury and clinical outcomes in patients undergoing on-pump coronary artery bypass graft surgery. No protective effects were noted in off-pump coronary artery bypass graft surgery.

Cannabinoid receptor type 2 activation yields delayed tolerance to focal cerebral ischemia.

We demonstrated in our previous research that pretreatment with electroacupuncture (EA) induces rapid (2h after EA) and delayed (24h after EA) tolerance to focal cerebral ischemia. We further elucidate the endocannabinoid and cannabinoid receptor type 1(CB1) involvment in the rapid ischemic tolerance induced by EA pretreatment. The present study aimed at investigating the involvement of the cannabinoid receptor type 2 (CB2) in the neuroprotection conferred by EA pretreatment. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 min at 2h and 24h following EA pretreatment in male Sprague-Dawley rats, respectively. Cerebral ischemic injury was evaluated by neurobehavioral scores and infarction volume percentages 72 h after reperfusion in the presence or absence of AM251, a selective CB1 receptor antagonist, and AM630, a selective CB2 receptor antagonist. The expression of CB1 and CB2 receptor in the striatum of ischemic hemisphere was also evaluated. The rapid and delayed ischemic tolerance induced by EA pretreatment was respectively reversed by AM251 and AM630. CB2 receptor expression was up-regulated in the striatum of rat brains at 24h after EA stimuli. These results indicate that CB2 receptor contributed to the delayed neuroprotective effect whereas CB1 receptor to the rapid ischemic tolerance induced by EA pretreatment against focal cerebral ischemia in rats.

Activation of epsilon protein kinase C-mediated anti-apoptosis is involved in rapid tolerance induced by electroacupuncture pretreatment through cannabinoid receptor type 1.

BACKGROUND AND PURPOSE: Our previous study has demonstrated that the rapid tolerance to cerebral ischemia by electroacupuncture (EA) pretreatment was possibly mediated through an endocannabinoid system-related mechanism. The purpose of this study was to investigate whether activation of epsilon protein kinase C (εPKC) was involved in EA pretreatment-induced neuroprotection via cannabinoid receptor type 1 in a rat model of transient focal cerebral ischemia. METHODS: The activation of εPKC in the ipsilateral brain tissues after EA pretreatment was investigated in the presence or absence of cannabinoid receptor antagonists. At 2 hours after the end of EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 minutes in rats. The neurobehavioral scores, infarction volumes, neuronal apoptosis, and the expression of Bcl-2 and Bax were evaluated after reperfusion in the presence or absence of εPKC-selective peptide inhibitor (TAT-εV1-2) or activator (TAT-ψεRACK). RESULTS: EA pretreatment enhanced εPKC activation. Systemic delivery of TAT-ψεRACK conferred neuroprotection against a subsequent cerebral ischemic event when delivered 2 hours before ischemia. Pretreatment with EA reduced infarct volumes, improved neurological outcome, inhibited neuronal apoptosis, and increased the Bcl-2-to-Bax ratio after reperfusion, and the beneficial effects were attenuated by TAT-εV1-2. In addition, the blockade of cannabinoid receptor type 1, but not cannabinoid receptor type 2 receptor, reversed the increase in εPKC activation and neuroprotection induced by EA pretreatment. CONCLUSIONS: EA pretreatment may activate endogenous εPKC-mediated anti-apoptosis to protect against ischemic damage after focal cerebral ischemia via cannabinoid receptor type 1, which represents a new mechanism of EA pretreatment-induced rapid tolerance to focal cerebral ischemia in rats.