Chemoselective Synthesis of 3-Bromomethyloxindoles via Visible-Light-Induced Radical Cascade Bromocyclization of Alkenes.

A novel visible-light-induced radical cascade bromocyclization of N-arylacrylamides has been accomplished. This reaction overcomes the overbromination at the benzene rings suffered in traditional electrophilic reactions, thus enabling the first highly chemoselective synthesis of valuable 3-bromomethyloxindoles. The combination of pyridine and anhydrous medium is identified as the key factor for the high chemoselectivity in the current photoreaction system, which might work by suppressing the in situ generation of low-concentration Br2 from N-bromosuccinimide. Moreover, the mild reaction conditions ensure the generation of a wide range of the new desired products with excellent functional group tolerance.

Decreased Innate Migration of Pro-Inflammatory M1 Macrophages through the Mesothelial Membrane Is Affected by Ceramide Kinase and Ceramide 1-P.

The retrograde flow of endometrial tissues deposited into the peritoneal cavity occurs in women during menstruation. Classically (M1) or alternatively (M2) activated macrophages partake in the removal of regurgitated menstrual tissue. The failure of macrophage egress from the peritoneal cavity through the mesothelium leads to chronic inflammation in endometriosis. To study the migration differences of macrophage phenotypes across mesothelial cells, an in vitro model of macrophage egress across a peritoneal mesothelial cell monolayer membrane was developed. M1 macrophages were more sessile, emigrating 2.9-fold less than M2 macrophages. The M1 macrophages displayed a pro-inflammatory cytokine signature, including IL-1α, IL-1ß, TNF-α, TNF-ß, and IL-12p70. Mass spectrometry sphingolipidomics revealed decreased levels of ceramide-1-phosphate (C1P), an inducer of migration in M1 macrophages, which correlated with its poor migration behavior. C1P is generated by ceramide kinase (CERK) from ceramide, and blocking C1P synthesis via the action of NVP231, a specific CERK chemical inhibitor, prohibited the emigration of M1 and M2 macrophages up to 6.7-fold. Incubation with exogenously added C1P rescued this effect. These results suggest that M1 macrophages are less mobile and have higher retention in the peritoneum due to lower C1P levels, which contributes to an altered peritoneal environment in endometriosis by generating a predominant pro-inflammatory cytokine environment.

Peroxiredoxin 6 mediates the protective function of curcumin pretreatment in acute lung injury induced by serum from patients undergoing one-lung ventilation in vitro.

BACKGROUND: Curcumin has attracted much attention due to its wide range of therapeutic effects. In this study, we used serum collected from patients undergoing one-lung ventilation (OLV) to establish an in vitro acute lung injury (ALI) model to explore the potential protective mechanism of curcumin on ALI. Our study provides a new reference for the prevention and treatment of ALI induced by OLV. METHODS: A549 cells were treated with 20% serum from patients undergoing OLV to establish an in vitro ALI model. Curcumin, at a dose of 40 µg/ml, was administered two hours prior to this model. The levels of inflammation and oxidative stress markers were observed by Western blot, qRT-PCR, ELISA and reactive oxygen species assay. Additionally, the expression of peroxiredoxin 6 (Prdx6) and proteins involved in the NF-κB signaling pathway was evaluated. RESULTS: Twenty percent of serum collected from patients undergoing OLV downregulated the expression of Prdx6, leading to the activation of the NF-κB signaling pathway, which was associated with the subsequent overproduction of inflammatory cytokines and reactive oxygen species. Pretreatment with curcumin restored Prdx6 downregulation and inhibited NF-κB pathway activation by suppressing the nuclear translocation of P65, eventually reducing inflammation and oxidative stress damage in A549 cells. CONCLUSIONS: Prdx6 mediated the protective function of curcumin by inhibiting the activation of the NF-κB pathway in ALI in vitro.

Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts.

Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. In this study, we evaluated whether morphine modulates cisplatin-induced apoptosis in human nasopharyngeal carcinoma CNE-2 cells and whether morphine affects the antitumor activity of cisplatin on tumor growth in human nasopharyngeal carcinoma CNE-2 xenografts in nude mice. We showed that a pretreatment with morphine (1 µg/ml) inhibited the sensitivity of CNE-2 cells to cisplatin by inhibiting cisplatin-induced CNE-2 cell apoptosis, decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. However, a high dose of morphine (1000 µg/ml) had the opposite effect. We also showed that at a low dose, morphine enhances chemoresistance in an in vivo nasopharyngeal carcinoma (NPC) model by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. Taken together, our results indicate that a low dose of morphine may lead to chemoresistance of cisplatin in NPC models in vitro and in vivo by inhibiting cisplatin-induced apoptosis and decreasing neovascularization.

The Application of THz Spectroscopy and GA-BP in Methanol Concentration Detection.

At ambient temperature and atmospheric pressure, making use of a photoconductive-antenna terahertz time-domain spectrograph and a self-designed air chamber, the terahertz time-domain spectroscopy (THz-TDS) technique test of methanol gas in the range of 0.1~3.0 THz shows that the methanol gas has no obvious absorption peaks in the range of 0.1~3.0 THz and has obvious absorption peaks in the range of 0.1~1.0 THz. In order to improve the determination accuracy of the concentration of the methanol gas, the author detected 15 groups of methanol gas with different concentrations on the basis of the relationship between the strengths of 15 characteristic absorption peaks of different locations and the concentration of the methanol gas, and obtained the difference curve of the of the characteristic absorption peaks. Based on the function approximation of BP neural network, the author optimized the initial weights and biases of the BP neural network by using the GA the genetic algorithm, which has higher rate of convergence to prevent from getting into local optimum easily, and constructed the mathematical model with the purpose of predicting the methanol gas concentration. The test results show that the neural network is applicable to predict methanol gas in the volume concentration range of 0.028 3~0.424 6 m3·L(-1), the average relative standard deviation of the 2 sets of samples is 1.7%, the average recovery rate is 98%, the error precision of the neural network is 10(-1), and correlation coefficient of the measured values and the predicted values is 0.996 77. The test basically achieved ideal predicted results. The research results obtained experimental data of methanol gas in the terahertz frequency band and found that the method of combining terahertz time-domain spectroscopy with GA-BP neural network can effectively detect the volume concentration of methanol gas, and provided a new method for the detection of concentration of methanol gas.

[Comparison of sevoflurane and propofol in combined anesthesia induction with remifentanil for tracheal intubation with fiberoptic bronchoscope].

OBJECTIVE: To compare the effect and hemodynamics of sevoflurane(SEV) and propofol (PRO) in combined anesthesia induction with remifentanil for tracheal intubation fibreoptic bronchoscope (FOB). METHODS: Twenty-four patients without difficult airway undergoing elective surgery with tracheal intubation general anesthesia were randomly divided into SEV and PRO group. FOB intubation was performed with sevoflurane or propofol administration combined with remifentanil induction. Blood pressure (BP), heart rate (HR), SPO2 and Narcotrend index (NI) were monitored to evaluate the anesthetic depth during the induction. The time to loss of consciousness (LOC), intubation time, intubation score, anesthetic dosage and adverse effects were recorded. RESULTS: No significant difference was found between the two groups in the time to LOC, intubation time, intubation score, remifentanil dosage. Intubation was performed successfully in both groups. BP and HR of both groups decreased after the induction and did not increase after the intubation, with variation within the normal range. No significant difference in BP and HR was found between the two groups. NI of both groups decreased after the induction and during intubation. NI of SEV group 2 min after intubation was higher than that of PRO group. There was no significant difference in NI between the two groups at the other time points. No significant adverse effects or recall of the intubation procedure were reported. CONCLUSION: Anesthesia induction FOB intubation with sevoflurane and propofol, both in combination with remifentanil, can be applied in surgical patients without contraindications to general anesthesia, and both methods can provide fast induction and good intubation condition with stable hemodynamics.

[Effects of midazolam premedication on induction doses of propofol and hemodynamic changes during tumor patient induction].

BACKGROUND AND OBJECTIVE: Midazolam is a useful drug used preoperatively because it can produce anxiolysis and sedation. This study compared the propofol requirements and haemodynamic effects during anaesthetic induction using propofol with premedication of midazolam or luminal. METHODS: Thirty patients (aged 20-65, ASA I-II) undergoing tumor surgery were randomly assigned into 2 groups (group M and group L): group M, receiving 0.5 mg atropine and 0.05 mg/kg midazolam; group L, receiving atropine and 2 mg/kg phenobarbital sodium 30 min before induction as premedication. Anesthesia was induced with propofol at the rate of 30 mg.kg-1.h-1 to achieve enough depth of anesthesia to intubate. Induction time, total propofol dosage, blood pressure, heart rate were recorded before and after induction, and after intubation. Awaken time was also recorded. RESULTS: The time of induction and the propofol dosage in group M (2.8 +/- 0.37 min and 79.9 +/- 15.3 mg) were significantly (P < 0.05) less than that in group L (3.3 +/- 0.54 min and 98.9 +/- 17.4 mg). Blood pressure was unchanged in M group after propofol induction and after the intubation. Heart rate change was much less in group M (P < 0.05). CONCLUSIONS: The results indicate that midazolam compered to phenobarbital sodium as premedication could reduce the usage of propofol, and also provide stable cardiovascular state during propofol induction.