Synthesis of the Macrolactone Cores of Maltepolides via a Diene-Ene Ring-Closing Metathesis Strategy.

Synthesis of the C19-truncated maltepolide E has been accomplished via a diene-ene ring-closing metathesis (RCM) strategy without damage to the C11-C14 alkenyl epoxy unit. Upon release of the C17-OH group, it attacked at the C14 position with double bond migration and epoxide ring opening to furnish the C19-truncated maltepolides A and B as proposed for the biosynthesis of maltepolides.

Predictive value of serum visinin-like protein-1 for early neurologic deterioration and three-month clinical outcome in acute primary basal ganglia hemorrhage: A prospective and observational study.

BACKGROUND: Visinin-like protein 1 (VILIP-1) appears as a biomarker of neuronal injury. We investigated the correlation of serum VILIP-1 concentrations with severity, early neurologic deterioration (END) and functional outcome of intracerebral hemorrhage (ICH). METHODS: In this prospective and observational study, serum VILIP-1 concentrations were quantified in 106 patients with basal ganglia hemorrhage. Univariate and multivariable logistic regression analyses were used to analyze the relationship between serum VILIP-1 concentrations and END plus worse prognosis (modified Rankin Scale score of 3 or greater) at post-injury 3 months. RESULTS: Serum VILIP-1 concentrations of patients were closely correlated with hematoma volume and National Institutes of Health Stroke Scale score. Serum VILIP-1 concentrations were substantially elevated in patients with END or worse 3-month prognosis, as compared to other remainders. Also, serum VILIP-1 concentrations were independently associated with END and worse 3-month prognosis. Under ROC curve analysis, serum VILIP-1 concentrations exhibited marked accuracy for distinguishing patients with the development of END or worse 3-month prognosis. Its predictive ability was in the range of hematoma volume and National Institutes of Health Stroke Scale score. CONCLUSIONS: Serum VILIP-1 may be a good biomarker for assessing hemorrhagic severity and clinical outcomes after ICH.

Measuring serum melatonin concentrations to predict clinical outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Oxidative stress has a key role in brain injury and melatonin possesses antioxidant effects. We aimed to ascertain the potential relationship between serum melatonin concentrations and functional outcome following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This prospective and observational study was conducted of 169 aSAH patients. Baseline serum melatonin concentrations were determined. A worse 6-month functional outcome was defined as a Glasgow Outcome Scale score of 1-3. RESULTS: Patients with a worse outcome (56 cases) compared to those with a good outcome (113 cases) exhibited significantly higher concentrations of serum melatonin (P < 0.001). An area under the receiver operating curve of 0.819 was revealed for the prediction of 6-month worse outcome by serum melatonin concentrations. Multiple logistic regression analysis showed an independent association of serum melatonin concentrations with 6-month worse outcome (odds ratio = 1.204). An intimate correlation existed between serum melatonin concentrations and World Federation of Neurological Surgeons subarachnoid hemorrhage scale scores as well as between serum melatonin concentrations and modified Fisher scores (P < 0.001). CONCLUSIONS: Patients with higher serum melatonin concentrations are more likely to have a poor prognosis. Serum melatonin can be considered as an independent predictor of functional outcome after aSAH.

Asymmetric Total Synthesis of the Highly Strained 4ß-Acetoxyprobotryane-9ß,15α-diol.

The first and asymmetric total synthesis of 4ß-acetoxyprobotryane-9ß,15α-diol, containing a rare and highly strained trans-fused bicyclo[3.3.0]octane ring system, has been achieved. The synthetically challenging [6-5-5] tricyclic ring system in the final product was efficiently and diastereoselectively synthesized via an asymmetric rhodium-catalyzed [4 + 2] cycloaddition reaction, followed by a unique benzilic acid type rearrangement under very mild conditions. The seven contiguous stereocenters were installed efficiently and diastereoselectively.

Intramolecular Diels-Alder Cycloaddition Approach toward the cis-Fused Δ5,6-Hexahydroisoindol-1-one Core of Cytochalasins.

Synthesis of the cis-fused Δ5,6-hexahydroisoindol-1-one core of cytochalasins B2-B5, K, Z8, Z9, Z12-Z15, and Z17 has been established starting from an intramolecular Diels-Alder reaction of the amide-tethered (8 E)-1,3,8-nonatriene. The trans-fused 5/6-bicyclic adduct was then subjected to highly stereoselective C9-ß-hydroxylation and epimerization of the C7-α-OH group.

Total Synthesis of Laingolide B Stereoisomers and Assignment of Absolute Configuration.

Total synthesis of (-)-(2 R,9 S)- and (+)-(2 S,9 S)-stereoisomers of laingolide B has been accomplished by using sequential ring-closing metathesis (RCM) and alkene isomerization to construct the macrocyclic trans- N-methyl enamide moiety. The Myers alkylation was used to secure the C2 stereochemistry of the two RCM precursors from a common (9 S)-C3-C9 alkyl iodide. The absolute configuration of laingolide B has been assigned as (2 S,9 R) by comparison of the optical rotation data.

Anti-epileptic Effects of Valepotriate Isolated from Valeriana jatamansi Jones and Its Possible Mechanisms.

OBJECTIVE: This work aimed to investigate the anti-epileptic effects of valepotriate isolated from Valeriana jatamansi Jones and studied its possible mechanisms. METHODS: The anti-epileptic effects of valepotriate were studied using maximal electroshock-induced seizure (MES), pentylenetetrazole (PTZ)-induced epilepsy, and pentobarbital sodium-induced sleeping model in mice. The possible anti-epileptic mechanisms of valepotriate were investigated by analyzing the expressions of GABAA, GABAB, glutamic acid decarboxylase (GAD65), Bcl-2, and caspase-3 in the brain using Western blot assay. RESULTS: The results indicated that valepotriate showed significant anti-epileptic activity against MES- and PTZ-induced epilepsy at doses of 5, 10, and 20 mg/kg, and ED50 values for MES- and PTZ-induced epilepsy were 7.84 and 7.19 mg/kg, respectively. Furthermore, valepotriate (10 and 20 mg/kg) can significantly prolong sleeping time and shorten the latency time on the pentobarbital sodium-induced sleeping time test. Furthermore, valepotriate (5, 10, and 20 mg/kg) could significantly up-regulate the expression of GABAA, GAD65, and Bcl-2 and down-regulate the expression of caspase-3, but had no significant effect on the expression of GABAB. CONCLUSION: The results indicated that valepotriate had anti-epileptic activity and the mechanisms might be associated with regulation of GABA and inhibition of neuronal apoptosis. SUMMARY: Anti-epileptic effect of valepotriate was investigated for the 1st timeValepotriate showed notable anti-epileptic activityValepotriate can significantly increase the expression of GABAA, glutamic acid decarboxylase 65, and Bcl-2 and reduce the expression of caspase-3.

Effects of microRNA-26b on proliferation and invasion of glioma cells and related mechanisms.

Neuroglioma is the most common primary malignant tumor in neurosurgery. Due to its short survival period and high patient mortality rate, neuroglioma is a major challenge in clinics. Elucidating the pathogenic mechanisms and associated molecular targets of neuroglioma can therefore benefit diagnosis and treatment of glioma. Previous studies have established the role of microRNA (miR)­26b in various tumors, including breast cancer, lymphoma and glioma. Its function and mechanism in neuroglioma, however, remains to be elucidated. In the present study, in vitro cultured U87 glioma cells were randomly divided into miR­26b mimic, miR­26b inhibitor and respective control (NC) groups. MTT assay was performed to detect the effect of miR­26b on cell proliferation, while a cell invasion assay detected its effects on cell invasion. Caspase­3 activity was also quantified to test cell apoptosis, followed by reverse transcription-quantitative polymerase chain reaction and western blotting to detect the variation of Bcl­2 expression under the effect of miR­26b. miR­26b mimics transfection upregulated its expression in U87 cells, which had significantly reduced Bcl­2 mRNA and protein expression levels and higher casapse3 activity, and inhibited cell proliferation and invasion compared with the control group. The transfection of miR­26b inhibitor, in contrast, facilitated U87 cell proliferation and invasion, inhibited caspase­3 activity and elevated Bcl­2 mRNA/protein expression. In conclusion, miR­26 could facilitate apoptosis and inhibit proliferation/invasion of neuroglioma cells via downregulating Bcl­2 expression and potentiating caspase-3 activity.

Role of galectin-3 in plasma as a predictive biomarker of outcome after acute intracerebral hemorrhage.

OBJECTIVE: Inflammation is involved in pathophysiological mechanisms underlying secondary brain injury after intracerebral hemorrhage. Enhanced circulating levels of galectin-3, a proinflammatory cytokine, have close relation to poor prognosis of some inflammatory illnesses. This study was designed to investigate whether plasma galectin-3 levels are related to the inflammation, severity and prognosis following intracerebral hemorrhage. METHODS: In this observational, prospective study, plasma galectin-3 levels of 110 patients and 110 controls were determined. We further assessed the association of galectin-3 levels with inflammation reflected by systemic C-reactive protein levels, severity indicated by hematoma volumes and National Institutes of Health Stroke Scale (NIHSS) scores, and endpoints including 1-week mortality, 6-month mortality, 6-month overall survival and 6-month unfavorable outcome (modified Rankin Scale score>2). RESULTS: Plasma galectin-3 levels of patients were significantly higher than those of controls. Galectin-3 was identified as an independent prognostic predictor for 1-week mortality, 6-month mortality, 6-month overall survival and 6-month unfavorable outcome, as well as had strong relation to C-reactive protein levels, hematoma volumes and NIHSS scores. Compared with NIHSS scores and hematoma volumes, plasma galectin-3 levels had similar areas under receiver operating characteristic curve (AUC). Moreover, galectin-3 levels significantly improved AUCs of NIHSS scores or hematoma volumes alone for prediction of 6-month mortality and 6-month unfavorable outcome. CONCLUSIONS: Elevated plasma galectin-3 levels are strongly associated with the inflammation, severity and poor prognosis after intracerebral hemorrhage, indicating galectin-3, involved in brain inflammation, might have the potential to be a prognostic biomarker for hemorrhagic stroke.

Microwave-Assisted Intramolecular Ullmann Diaryl Etherification as the Post-Ugi Annulation for Generation of Dibenz[b,f][1,4]oxazepine Scaffold.

A sequence of the Ugi four-component reaction (U-4CR) and microwave-assisted intramolecular Ullmann etherification has been established for efficient generation of a dibenz[b,f][1,4]oxazepine scaffold. The U-4CR, using 2-aminophenols and 2-bromobenzoic acids or 2-bromobenzaldehydes as the inputs, was carried out in MeOH at 50-60 °C for 2-3 days to form a collection of 22 linear products in 46-90% yields. A microwave-assisted intramolecular Ullmann etherification was then used to transform these acyclic U-4CR products into the cleft-shaped 6/7/6-fused tricyclic heterocycles. The intramolecular Ullmann diaryl ether formation was catalyzed by 10 mol % of CuI and 30 mol % of N,N-dimethylglycine hydrochloride (DMG·HCl) in the presence of Cs2CO3 with microwave irradiation (150 °C, 30 min) to furnish dibenz[b,f][1,4]oxazepin-11(10H)-ones and dibenz[b,f][1,4]oxazepin-11(10H)-carboxamides in 64-100% yields.

Ertapenem prophylaxis of surgical site infections in elective colorectal surgery in China: a multicentre, randomized, double-blind, active-controlled study.

OBJECTIVES: Our purpose was to evaluate ertapenem versus ceftriaxone/metronidazole for prophylaxis of surgical site infections (SSIs) following elective colorectal surgery in Chinese adult patients. METHODS: Eligible Chinese adults aged 18-80 years scheduled to undergo elective colorectal surgery by laparotomy were randomized to receive a 30 min infusion of 1 g of ertapenem/metronidazole placebo or 2 g of ceftriaxone/500 mg of metronidazole within 2 h before initial incision. The study endpoint was the proportion of patients with successful prophylaxis at 4 weeks after treatment. The primary analysis was based on the evaluable population (PP population) and the pre-specified non-inferiority margin was set at -15%. ClinicalTrials.gov: NCT01254344. RESULTS: Of 599 patients randomized, 499 (251 ertapenem and 248 ceftriaxone) were eligible for inclusion in the PP population. The proportions of patients with successful prophylaxis in the ertapenem and ceftriaxone groups were 90.4% (227/251) and 90.3% (224/248), respectively. The difference in the proportion of successful outcomes was 0.1% (95% CI -5.2%, 5.5%). Unexplained antibiotic use was the most frequent reason for prophylaxis failure in both groups [ertapenem 4.8% (12/251), ceftriaxone 4.4% (11/248); difference 0.3%; 95% CI -3.6, 4.3]. Pathogen species isolated from SSI sources were consistent with previously conducted studies and the product package insert. The incidence of adverse events (AEs) was similar between the groups, with the most common AE being pyrexia [ertapenem 7.6% (22/290), ceftriaxone 5.7% (17/297)]. CONCLUSIONS: Ertapenem is as effective as ceftriaxone/metronidazole for SSI prophylaxis in patients undergoing elective colorectal surgery, and is well tolerated.

Downregulation of LKB1 suppresses Stat3 activity to promote the proliferation of esophageal carcinoma cells.

The tumor suppressor liver kinase B1 (LKB1) encodes a serine/threonine kinase. The defect in LKB1 is the primary cause of Peutz-Jeghers syndrome (PJS). Inactivation of LKB1 by mutations or loss of LKB1 expression is associated with ovarian, lung and pancreatic cancer; however, the correlation between LKB1 and esophageal carcinoma remains unknown. Thus, quantitative PCR was performed to determine the clinical significance of LKB1 expression in 60 cases of esophageal cancer and its adjacent normal epithelium. LKB1 expression was observed to significantly downregulate the accompanying cancer progression, which was verified at the protein level by western blot analysis. Furthermore, the phosphorylated signal transducer and activator of transcription 3 (Stat3) level is reversibly associated with LKB1 expression. To determine the function of LKB1 in esophageal cancer, LKB1 expression is induced in TE1 esophageal cancer cells. The results show that LKB1 overexpression suppresses the proliferation of TE1 cells, downregulates the expression of cyclin D1 and Myc and represses Stat3 phosphorylation. Suppression of cell proliferation and cyclin D1 expression by LKB1 is fully inhibited by constitutively active Stat3C coexpression, suggesting that LKB1 inhibits esophageal cancer cell proliferation through suppression of Stat3 transaction. In conclusion, downregulation of LKB1 expression suppresses Stat3 activity that may promote tumor growth during esophageal cancer progression.

Leptin as a marker for severity and prognosis of aneurysmal subarachnoid hemorrhage.

Leptin has been identified as a plasma marker for outcomes in traumatic brain injury and intracerebral hemorrhage. We further investigated whether leptin might serve as a marker for severity and prognosis in aneurysmal subarachnoid hemorrhage. One hundred and eight consecutive patients and 108 sex and age - matched healthy subjects were recruited. Plasma leptin levels were measured by enzyme-linked immunosorbent assay. Clinical severity was assessed using World Federation of Neurological Surgeons score and Fisher score. Mortality and poor long-term outcome (Glasgow outcome scale scores of 1-3) at 6 months were recorded. Plasma leptin levels on admission were substantially higher in patients than in healthy controls, and were significantly associated with the clinical severity. There was also a significant association between leptin levels and clinical outcomes at 6 months in multivariate logistic regression analysis. Using receiver operating characteristic curves, we calculated areas under the curve for clinical outcomes at 6 months. The predictive performance of leptin was similar to, but did not obviously improve those of World Federation of Neurological Surgeons score and Fisher score. Thus, leptin may indicate clinical severity of the initial bleeding and also have prognostic value for clinical outcomes in aneurysmal subarachnoid hemorrhage and may therefore help in guiding treatment decisions in the setting of aneurysmal subarachnoid hemorrhage.

Association between folate intake, serum folate levels and the risk of lung cancer: a systematic review and meta-analysis.

BACKGROUND: Folate plays a critical role in nucleotide synthesis and DNA methylation, and was considered to be associated with anti-carcinogenesis. RESULTS: from studies that concern the relationship between the folate intake or serum folate levels and lung cancer risk showed no consistency, which requires our further comprehensive meta-analysis. METHODS: Systematic literature search was conducted to identify the relevant studies (published prior to February 2013) according to standard protocol. Estimated effects were calculated under both random-effects and fixed-effects models. Heterogeneity between studies and publication bias were also evaluated. RESULTS: A total of 4390 cases and 6138 controls from 6 case-control studies revealed a significant overall inverse association between folate intake and lung cancer risk (OR = 0.74, 95%CI = 0.65 - 0.84, P < 0.001). Summary of 1438 cases and 2582 controls from 4 case-control studies and 44 cases out of a cohort of 1988 participants suggested a marginal association without significance (OR = 0.78, 95%CI = 0.60 - 1.02, P = 0.075) between high serum folate levels and less lung cancer susceptibility; however, subgroup analysis about population-based case-control studies showed that high serum folate levels significantly associated with the reduced lung cancer risk (OR = 0.76, 95%CI = 0.58 - 1.00, P = 0.048). CONCLUSION: Higher folate intake can be a protective factor against lung cancer risk, and higher serum folate level is probably associated with reduced lung cancer risk in marginal manner, though more studies are warranted to confirm these associations.

Increased plasma 8-iso-prostaglandin F2α concentration in severe human traumatic brain injury.

BACKGROUND: 8-Iso-Prostaglandin F2α (8-iso-PGF2α) is considered as a gold standard for measuring oxidative stress in vivo. The present study was undertaken to investigate plasma 8-iso-PGF2α concentrations in severe human traumatic brain injury (TBI) and to analyze its correlation with disease outcome. METHODS: One hundred six healthy subjects and 106 severe TBI patients were recruited. The correlations of plasma 8-iso-PGF2α concentration with 1-year mortality and unfavorable outcome (Glasgow Outcome Scale score of 1-3) were analyzed. RESULTS: Thirty-one patients (29.2%) died and 48 patients (45.3%) had an unfavorable outcome at 1 year after TBI. Patients had significantly higher plasma 8-iso-PGF2α levels compared to healthy controls (572.1±157.5 pg/ml vs. 84.3±18.9 pg/ml, P<0.001). A multivariate analysis selected plasma 8-iso-PGF2α level as an independent predictor for 1-year unfavorable outcome [odds ratio (OR) 1.401, 95% confidence interval (CI) 1.107-2.371, P=0.005] and mortality (OR 1.609, 95% CI 1.113-3.142, P=0.003). A receiver operating characteristic curve analysis showed plasma 8-iso-PGF2α level predicted 1-year unfavorable outcome [area under curve (AUC), 0.871; 95% CI, 0.792-0.928] and mortality (AUC, 0.881; 95% CI, 0.804-0.936) as statistically significantly. The prognostic value of 8-iso-PGF2α was similar to that of Glasgow Coma Scale score for 1-year clinical outcomes (both P>0.05). However, 8-iso-PGF2α did not improve the prognostic value of Glasgow Coma Scale score for 1-year clinical outcomes (both P>0.05). CONCLUSIONS: Plasma 8-iso-PGF2α level is highly associated with 1-year clinical outcomes of TBI.

High concentrations of visfatin in the peripheral blood of patients with acute basal ganglia hemorrhage are associated with poor outcome.

Higher plasma visfatin concentration has been associated with clinical outcomes of traumatic brain injury. No published information exists to date about change in plasma visfatin after intracerebral hemorrhage. This study included one hundred and twenty-eight healthy controls and 128 patients with intracerebral hemorrhage. The unfavorable outcome was defined as modified Rankin Scale score >2 at 6 months. The patients had higher plasma visfatin measurements than control subjects. Plasma visfatin levels were highly correlated with National Institutes of Health Stroke Scale score and plasma C-reactive protein levels in the patients. A multivariate analysis identified plasma visfatin level as an independent predictor for 6-month mortality and unfavorable outcome. According to receiver operating characteristic curve analysis, the predictive value of the plasma visfatin concentration was similar to National Institutes of Health Stroke Scale score. In a combined logistic-regression model, visfatin improved the predictive value of National Institutes of Health Stroke Scale score for 6-month unfavorable outcome. Thus, increased plasma visfatin level is associated with 6-month clinical outcomes after intracerebral hemorrhage.

Prognostic value of copeptin: one-year outcome in patients with traumatic brain injury.

High plasma copeptin level has been associated with one-month mortality after traumatic brain injury. However, not much is known regarding its relation with long-term outcome. Thus, we investigated the ability of copeptin to predict 1-year outcome in patients with traumatic brain injury. One hundred and six healthy controls and 106 patients with acute severe traumatic brain injury were included. Plasma samples were obtained on admission. Its concentration was measured by enzyme-linked immunosorbent assay. Forty-eight patients (45.3%) suffered from unfavorable outcome (Glasgow Outcome Scale score of 1-3) and 31 patients (29.2%) died in 1 year after traumatic brain injury. Upon admission, plasma copeptin level in patients was substantially higher than that in healthy controls. A forward stepwise logistic regression selected plasma copeptin level as an independent predictor for 1-year unfavorable outcome and mortality of patients. A receiver operating characteristic curve analysis showed plasma copeptin level predicted 1-year unfavorable outcome and mortality obviously. The predictive value of the copeptin concentration was thus similar to that of Glasgow Coma Scale score for the prediction of unfavorable outcome and mortality after 1 year. In a combined logistic-regression model, copeptin improved the area under curve of Glasgow Coma Scale score for the prediction of unfavorable outcome and mortality after 1 year, but the differences were not significant. Thus, copeptin level is a useful, complementary tool to predict functional outcome and mortality 1 year after traumatic brain injury.

[Preliminary application study of Ligasure in video-assisted thoracic pulmonary surgery].

OBJECTIVE: To investigate the application and techniques of Ligasure in video-assisted thoracic pulmonary surgery. METHODS: Use Ligasure to dissect lung parenchyma, small pulmonary vessel and stop bleeding in 15 cases spontaneous pneumothorax and 20 cases peripheral single lung node who undertaken video-assisted thoracic surgery during October 2008 to June 2010. RESULT: All the procedures were successful, no severe complications, as active bleeding, continuous air leak occurred. A period of 9.3 months (2 - 18 months) follow-up of all patients shows no delayed bleeding or recurrence pneumothorax. CONCLUSION: Ligasure is safe, easy to use. It can optimize operation and reduce the operation time.

2-Amino-6-methyl-pyridinium 4-nitro-benzoate.

In the crystal structure of the title salt, C(6)H(9)N(2) (+)·C(7)H(4)NO(4) (-), the cations and anions are linked by N-H⋯O hydrogen bonds, forming chains running parallel to the b axis.