Reactive Dicarbon as a Flexible Ligand for Transition-Metal Coordination and Catalysis.

Dicarbon is a reactive carbon allotrope that naturally exists only in the high-temperature medium of stellar space. We report the successful preparation of a series of bottleable phosphine-stabilized dicarbon (PDC) molecules. We explore the use of these molecules as a new complementary class of carbene-like ligands featuring strong σ-donor (>NHCs and CAAcs) but weak π-acceptor properties. Steric map analysis of PDC based on Cavallo's SambVca program reveals comparable steric volume bulk of 32.5%, similar to the conventional IMes carbene. However, our PDCs exhibit dynamic steric flexibility modulated by the nature of the metal complexes and catalytic reaction environment. We demonstrate the catalytic utility of the PDC framework by its successful implementation for Suzuki-Miyaura cross-coupling and the reductive coupling reaction of an aldehyde and alkyne. Detailed investigations of the reductive coupling reaction reveal an important secondary interaction between PDC and metal complexes, which plays a critical role in the catalytic system.

Etomidate plus propofol versus propofol alone for sedation during gastroscopy: a randomized prospective clinical trial.

BACKGROUND AND AIMS: Sedation with propofol alone during gastroscopy has many side effects. Etomidate has advantages in terms of circulation and respiration compared to propofol. We hypothesized that etomidate plus propofol during gastroscopy would be more safe and effective than propofol alone. METHODS: Four hundred (n = 400) patients were randomly divided into a propofol group (P group) and a etomidate plus propofol group (EP group). The P group was given the first dose of 1 % propofol 1 mg/kg before gastroscopy, and the EP group was given 1 % propofol 0.5 mg/kg plus etomidate 0.1 mg/kg. Repeated doses of 10-20 mg propofol or 5-10 mg propofol plus 1-2 mg etomidate were administered to maintain an adequate level of sedation. The sedation depth was maintained by bispectral index value of 40-60. RESULTS: The EP group had a lower incidence of systolic hypotension (13.0 vs. 32.5 %; P < 0.0001), bradycardia (8.5 vs. 16.5 %; P = 0.0226), mild hypoxemia (6.5 vs. 18.0 %; P = 0.0007), and severe hypoxemia (2.5 vs. 10.0 %; P = 0.0031) compared to the P group. Also, the satisfaction of anesthetist and gastroscopist with EP was higher than that of P group (P < 0.0001; P = 0.018, respectively). CONCLUSION: Etomidate plus propofol had few effects on respiration and circulation in patients undergoing gastroscopy and was more safe and effective than propofol alone.

Cannabinoid CB2 Receptor Mediates Nicotine-Induced Anti-Inflammation in N9 Microglial Cells Exposed to ß Amyloid via Protein Kinase C.

BACKGROUND: Reducing ß amyloid- (Aß-) induced microglial activation is considered to be effective in treating Alzheimer's disease (AD). Nicotine attenuates Aß-induced microglial activation; the mechanism, however, is still elusive. Microglia could be activated into classic activated state (M1 state) or alternative activated state (M2 state); the former is cytotoxic and the latter is neurotrophic. In this investigation, we hypothesized that nicotine attenuates Aß-induced microglial activation by shifting microglial M1 to M2 state, and cannabinoid CB2 receptor and protein kinase C mediate the process. METHODS: We used Aß1-42 to activate N9 microglial cells and observed nicotine-induced effects on microglial M1 and M2 biomarkers by using western blot, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that nicotine reduced the levels of M1 state markers, including inducible nitric oxide synthase (iNOS) expression and tumor necrosis factor α (TNF-α) and interleukin- (IL-) 6 releases; meanwhile, it increased the levels of M2 state markers, including arginase-1 (Arg-1) expression and brain-derived neurotrophic factor (BDNF) release, in the Aß-stimulated microglia. Coadministration of cannabinoid CB2 receptor antagonist or protein kinase C (PKC) inhibitor partially abolished the nicotine-induced effects. CONCLUSION: These findings indicated that cannabinoid CB2 receptor mediates nicotine-induced anti-inflammation in microglia exposed to Aß via PKC.

Neuroprotective effects of viral overexpression of microRNA-22 in rat and cell models of cerebral ischemia-reperfusion injury.

Several studies have reported that microRNA (MIR) is involved in the pathogenesis and progression of ischemic diseases, including cerebral ischemia, and that MIR-22 may inhibit the inflammatory response and cell apoptosis, which contribute to ischemia/reperfusion (I/R) injury. However, the specific function of MIR-22 in cerebral I/R injury remains far from clear. This study aimed to examine the potential protective effect of MIR-22 against cerebral I/R injury and its mechanism. As predicted, adenovirus-mediated MIR-22 overexpression markedly reduced the neurological score and infarct size (P < 0.05). We demonstrated that MIR-22 overexpression resulted in a reduction in inflammatory cytokines TNF-α, IL-6, COX-2, and iNOS, whereas the level of IL-10 was enhanced. MIR-22 overexpression significantly inhibited NF-κB activity by decreasing NF-κB coactivator NCOA1 expression. Furthermore, we found that MIR-22 could reduce the apoptotic rate of cortical neurons. Caspase-3 activity was inhibited by MIR-22, and the expression of the anti-apoptosis gene Bcl-2 in neurons was increased and that of the pro-apoptosis gene Bax decreased following MIR-22 overexpression. Our results suggest that MIR-22 could be used to treat cerebral I/R injury and that its neuroprotective effect may be attributed to a reduction in inflammation and apoptosis.

Mannitol improves cerebral oxygen content and postoperative recovery after prolonged retroperitoneal laparoscopy.

BACKGROUND: Prolonged pneumoperitoneum has cerebral adverse effects that may delay recovery and cause postoperative cognitive changes. The purpose of this study was to investigate the effect of mannitol infusion after pneumoperitoneum initiation on cerebral oxygen balance and quality of postoperative recovery in patients undergoing prolonged retroperitoneal laparoscopy. METHODS: Forty patients scheduled for retroperitoneal laparoscopic radical excision of prostatic carcinoma were randomly divided into two groups (n = 20, each) to receive either 0.5 g/kg of 20% mannitol 150 min after the initiation of pneumoperitoneum or an equal volume of 0.9% normal saline. After surgery, time to extubation and recovery time were recorded. The Observer's Assessment of Alertness/Sedation (OAA/S) scale was used to assess the quality of recovery. The Mini-Mental State Exam (MMSE) was given to test cognitive function preoperatively and at 1, 2, and 3 h after extubation. Blood samples from the jugular bulb and the radial artery were collected for blood gas analysis before CO2 insufflation and at 10, 60, and 180 min after insufflation. RESULTS: In the control group (without mannitol), the difference between arterial and venous oxygen content (CaO2-CvO2) before insufflation (6.21 ± 2.58 mL/dL) was significantly greater than it was 3 h after insufflation (2.63 ± 1.29 mL/dL; p < 0.05). Furthermore, 3 h after insufflation, the CaO2-CvO2 also was higher in the group that had been administered mannitol (5.93 ± 1.98 mL/dL) than it was in the control group at that time (p < 0.05). Lactic acid in both arterial and jugular venous blood of the control group at 3 h postinsufflation (2.39 ± 0.89 and 2.51 ± 0.72 mg/dL, respectively) had increased significantly from the preinsufflation values (1.18 ± 0.82 and 1.1 ± 0.85 mg/dL). In the group that received mannitol, the lactic acid levels 3 h postinsufflation were essentially the same as the preinsufflation values. The recovery and extubation times in those receiving mannitol (12.19 ± 2.12 and 20.14 ± 3.62 min, respectively) were significantly shorter than in the control group (21.25 ± 3.61 and 28.79 ± 4.73 min; p < 0.05). The OAAS scores of the mannitol group at the time of extubation and 10 min afterward was significantly higher than these scores in the control group (p < 0.05). One hour and 2 h after extubation, the cognitive function score of the mannitol group was significantly higher than for the control group (p < 0.05). CONCLUSIONS: After prolonged retroperitoneal laparoscopy, there is an imbalance between oxygen supply and demand. A small dose of mannitol can effectively improve cerebral oxygen metabolism, recovery, and cognitive function after the operation.

Antitubercular chromones and flavonoids from Pisonia aculeata.

Three new chromones, pisonins A (1), B (2), and D (4), two new flavonoids, pisonivanone [(2S)-5,7,2'-trihydroxy-8-methylflavanone] (7) and pisonivanol [(2R,3R)-3,7-dihydroxy-5,6-dimethoxyflavanone] (8), one new isoflavonoid, pisonianone (5,7,2'-trihydroxy-6-methoxy-8-methylisoflavone) (9), and five compounds first isolated from nature, namely, pisonins C (3), E (5), and F (6), pisoniamide (10), and pisonolic acid (11), together with 18 known compounds have been isolated from the methanol extract of the combined stem and root of Pisonia aculeata. Among these isolates, 2, 7, 14, 16, and 19 exhibited antitubercular activities (MICs≤50.0 µg/mL) against Mycobacterium tuberculosis H37Rv in vitro.

Isolable dicarbon stabilized by a single phosphine ligand.

In contrast to naturally occurring F2, O2 and N2, diatomic C2 is an intriguing species that has only been observed indirectly in the gas phase, and because of its high reactivity has eluded isolation in the condensed phase. It has previously been stabilized in L→C2←L compounds but the bonding situation of the central C2 in this motif differs remarkably from that of free C2. Here we have prepared and structurally characterized diatomic C2 as a monoligated complex L→C2 using a bulky phosphine ligand bearing two imidazolidin-2-iminato groups (L is (NHCR=N)2(CH3)P, where NHCR is an N-heterocyclic carbene). The compound is stable in solution at ambient temperature and has also been isolated in the solid state. Reactivity studies, in combination with quantum chemical analysis, suggest that the two carbon atoms of the L→C2 complex both have carbene character. The complex underwent intermolecular C-H bond activation upon thermolysis and exhibited hydroalkoxylation-like reactivity with methanol.

SOD2 Mediates Amifostine-Induced Protection against Glutamate in PC12 Cells.

BACKGROUND: Cytoprotectant amifostine attenuates radiation-induced oxidative injury by increasing intracellular manganese superoxide dismutase (SOD2) in peripheral tissue. However, whether amifostine could protect neuronal cells against oxidative injury has not been reported. The purpose of this study is to explore the protection of amifostine in PC12 cells. METHODS: PC12 cells exposed to glutamate were used to mimic neuronal oxidative injury. SOD assay kit was taken to evaluate intracellular Cu/Zn SOD (SOD1) and SOD2 activities; western blot analysis and immunofluorescence staining were performed to investigate SOD2 protein expression; MTT, lactate dehydrogenase (LDH), release and cell morphology were used to evaluate cell injury degree, and apoptotic rate and cleaved caspase-3 expression were taken to assess apoptosis; mitochondrial superoxide production, intracellular reactive oxygen species (ROS), and glutathione (GSH) and catalase (CAT) levels were evaluated by reagent kits. RESULTS: Amifostine increased SOD2 activity and expression, decreased cell injury and apoptosis, reduced mitochondrial superoxide production and intracellular ROS generation, and restored intracellular GSH and CAT levels in PC12 cells exposed to glutamate. SOD2-siRNA, however, significantly reversed the amifostine-induced cytoprotective and antioxidative actions. CONCLUSION: SOD2 mediates amifostine-induced protection in PC12 cells exposed to glutamate.

Cannabinoid receptor CB1 is involved in nicotine-induced protection against Aß1-42 neurotoxicity in HT22 cells.

Emerging evidences suggest that nicotine exerts a neuroprotective effect on Alzheimer's disease (AD), yet the precise mechanism is not fully elucidated. Here, HT22 cells were exposed to amyloid beta protein fragment (Aß)1-42 to mimic the pathological process of neuron in AD. We hypothesized that cannabinoid receptor CB1 is involved in the nicotine-induced neuroprotection against Aß1-42 injury in HT22 cells. CB1 expression in HT22 cells was investigated by immunocytochemistry and Western blot. The injury of HT22 cells was evaluated by cellular morphology, cell viability, and lactate dehydrogenase (LDH) release. The apoptosis of HT22 cells was assessed by flow cytometry and expressions of Bcl-2 and Bax. The results demonstrated that nicotine markedly upregulated CB1 expression, increased cell viability, ameliorated cellular morphology, decreased LDH release, and reduced the apoptotic rate of HT22 cells exposed to Aß1-42 for 24 h, while the blockade of CB1 or the inhibition of protein kinase C (PKC) partially reversed the neuroprotection. Furthermore, the blockade of CB1 reversed nicotine-induced PKC activation in HT22 cells exposed to Aß1-42. These results suggest that CB1 is involved in the nicotine-induced neuroprotection against Aß1-42 neurotoxicity, and the neuroprotection may be dependent on the activation of PKC.

Serum adropin levels are decreased in patients with acute myocardial infarction.

OBJECTIVE: Adropin is a recently identified bioactive protein that is important for energy homeostasis and maintaining insulin sensitivity. We sought to detect serum adropin levels in acute myocardial infarction (AMI) patients. METHODS: We enrolled 138 AMI patients, 114 stable angina pectoris (SAP) patients and 75 controls. Adropin levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum adropin levels were significantly lower in patients with AMI compared with SAP patients or controls (P<0.01). Multivariate logistic regression demonstrated that lower adropin was the independent predictor for the presence of AMI in coronary artery disease (CAD) patients (P<0.01). Serum adropin levels were negatively associated with body mass index (BMI) (P<0.01) and triglyceride levels (P<0.05) in AMI patients. CONCLUSION: Decreased serum adropin levels are associated with the presence of AMI in CAD patients. These results revealed that adropin might represent as a novel biomarker for predicting AMI onset in CAD patients.

Anandamide protects HT22 cells exposed to hydrogen peroxide by inhibiting CB1 receptor-mediated type 2 NADPH oxidase.

BACKGROUND: Endogenous cannabinoid anandamide (AEA) protects neurons from oxidative injury in rodent models; however the mechanism of AEA-induced neuroprotection remains to be determined. Activation of neuronal NADPH oxidase 2 (Nox2) contributes to oxidative damage of the brain, and inhibition of Nox2 can attenuate cerebral oxidative stress. We aimed to determine whether the neuronal Nox2 was involved in protection mediated by AEA. METHODS: The mouse hippocampal neuron cell line HT22 was exposed to hydrogen peroxide (H2O2) to mimic oxidative injury of neurons. The protective effect of AEA was assessed by measuring cell metabolic activity, apoptosis, lactate dehydrogenase (LDH) release, cellular morphology, intracellular reactive oxygen species (ROS), and antioxidant and oxidant levels and Nox2 expression. RESULTS: HT22 cells exposed to H2O2 demonstrated morphological changes, decreased LDH release, reduced metabolic activity, increased levels of intracellular ROS and oxidized glutathione (GSSG), reduced levels of superoxide dismutase (SOD), and reduced glutathione (GSH) and increased expression of Nox2. AEA prevented these effects, a property abolished by simultaneous administration of CB1 antagonist AM251 or CB1-siRNA. CONCLUSION: Nox2 inhibition is involved in AEA-induced cytoprotection against oxidative stress through CB1 activation in HT22 cells.

Serum S100A12 levels are correlated with the presence and severity of coronary artery disease in patients with type 2 diabetes mellitus.

OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) are at high risk for development of atherosclerosis and cardiovascular events. Serum S100A12 levels have been reported to be associated with coronary artery disease (CAD) and T2DM. We sought to assess whether serum S100A12 levels are correlated with the presence and severity of CAD. METHODS: Type 2 diabetes mellitus levels in 188 consecutive patients with T2DM undergoing coronary angiography for the evaluation of CAD. The severity of CAD was assessed by the Coronary Atherosclerosis Index (CAI) scores. RESULTS: Serum S100A12 levels were significantly higher in patients with T2DM with CAD than in those without CAD. Multivariate logistic regression analysis revealed that serum S100A12 levels were independently associated with the presence of CAD. Serum S100A12 levels were positively correlated with the Coronary Atherosclerosis Index scores after adjusting for other clinical characteristics. CONCLUSION: High S100A12 levels are associated with the presence and severity of CAD in patients with T2DM.

Preconditioning with isoflurane produces dose-dependent neuroprotection via activation of adenosine triphosphate-regulated potassium channels after focal cerebral ischemia in rats.

UNLABELLED: In this study, we determined whether repeated brief isoflurane (Iso) anesthesia induces ischemic tolerance to focal cerebral ischemia in a dose-response manner and whether the effect is dependent on adenosine triphosphate-regulated potassium channels. In Experiment 1, 40 rats were randomly assigned to 4 groups: control animals received 100% oxygen 1 h/d for 5 days, whereas the isoflurane (Iso)1, Iso2, and Iso3 groups received 0.75%, 1.5%, or 2.25% Iso in oxygen 1 h/d for 5 days. In Experiment 2, 36 rats were randomly assigned to 4 groups: controls received 100% oxygen 1 h/d for 5 days; animals in the Iso and I+G (Iso+glibenclamide) groups received 2% Iso in oxygen 1 h/d for 5 days, and the I+G group received glibenclamide (GLB) (5 mg/kg intraperitoneally) before each Iso pretreatment. Animals in the GLB group received GLB (5 mg/kg intraperitoneally) once a day for 5 days. Twenty-four hours after the last pretreatment, the right middle cerebral artery was occluded for 120 min. Neurologic deficit scores (NDS) and brain infarct volumes were evaluated at 24 h. The NDS and infarct volumes of Iso2 and Iso3 were less than those of the controls (P < 0.05). The infarct volume in Iso3 was smaller than in Iso2 (P < 0.05). The NDS and infarct volume in the Iso group were less than in the control and I+G groups (P < 0.05). There was no statistical difference among the control, I+G, and GLB groups. The study demonstrated that repeated Iso anesthesia induces ischemic tolerance in rats in a dose-response manner. GLB, an adenosine triphosphate-regulated potassium channel blocker, abolished the tolerance induced by Iso. IMPLICATIONS: Brief isoflurane anesthesia induces ischemic tolerance in the brain. The effect was found to be dose dependent in a rat focal cerebral ischemia model. Ischemic tolerance induced by isoflurane preconditioning is dependent on activation of adenosine triphosphate-regulated potassium channels.